READING ASSIGNMENT 1 (HOSPITAL MANAGEMENT MANUAL OF DOH)

ASHP GUIDELINES: MINIMUM STANDARD FOR PHARMACIES IN HOSPITALS

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PSHP STATEMENT OF MINIMUM STANDARD FOR HOSPITAL PHARMACY PRACTICE

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PHARMACY AND THERAPEUTICS COMMITTEE

ASHP GUIDELINES ON THE PHARMACY AND THERAPEUTICS COMMITTEE AND FORMULARY SYSTEM

ASHP Guidelines on the Pharmacy and Therapeutics Committee and the Formulary System (pre-press
version)* Christy Ciccarello, PharmD, MHA Vice President, Clinical Pharmacy Services Novant Health
Winston-Salem, NC Molly Billstein Leber, PharmD, BCPS, FASHP Associate Director, Drug Use Policy and
Formulary Management Yale New Haven Health System New Haven, CT Mandy C. Leonard, PharmD,
BCPS System Director, Drug Use Policy and Formulary Management Department of Pharmacy Cleveland
Clinic Cleveland, OH Todd Nesbit, PharmD, MBA, FASHP Director of Pharmacy Patient Care Services The
Johns Hopkins Health System Baltimore, MD Mary G. Petrovskis, PharmD, BCPS PGY2 Health-System
Pharmacy Administration Resident University of North Carolina Medical Center Chapel Hill, NC Emily
Pherson, PharmD, BCPS Assistant Director, Medication Use Policy & Clinical Informatics The Johns
Hopkins Health System Baltimore, MD Heidi A. Pillen, PharmD, FASHP Director of Pharmacy, Clinical
Services & Medication Use Policy Beaumont Health Southfield, MI Celia Proctor, PharmD, MBA Assistant
Director, System Formulary Management & Integration The Johns Hopkins Health System Baltimore, MD
Jennifer Reddan, PharmD, FASHP Pharmacy Executive Director, Excelerate Vizient Irving, TX ASHP
Guidelines on the P&T Committee and the Formulary System (pre-press) 2 Purpose These guidelines
outline important considerations and recommend processes for formulary system management within
the context of a hospital or health system. Pharmacist responsibilities and roles in managing the
formulary system in partnership with other healthcare professionals are embedded throughout. These
guidelines also provide assistance to pharmacists in the organization and operation of the pharmacy and
therapeutics (P&T) committee or equivalent body, evaluation of medications for formularies and
consideration of rational use of medications, and development and implementation of strategies to
optimize medication use through the formulary system. A glossary of terms is provided in Appendix A.
Formulary and formulary system A formulary is a continually updated list of available medications and
related information, representing the clinical judgment, resulting from a review of the clinical evidence,
of physicians, pharmacists, and other clinicians in the diagnosis, prophylaxis, or treatment of disease and
promotion of health. A formulary includes, but is not limited to, a list of medications and medication-
associated products or devices, medication-use policies, important ancillary drug information, decision-
support tools, and organizational guidelines. A formulary system is the ongoing process through which a
healthcare organization establishes policies regarding the use of drugs, therapies, and drug-related
products, including medication delivery devices, and identifies those that are most medically
appropriate, safe, and cost-effective to best serve the health interests of a given patient population.1
Formulary systems are used in many different settings, including hospitals, acute care facilities, home
care settings, and long- ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 3
term-care facilities, as well as by payers such as Medicare, Medicaid, insurance companies, and
managed care organizations. Many organizations have policy statements on the use of formularies.2-8
These guidelines focus on the use of formulary systems in hospitals and health systems, in both
inpatient and outpatient settings. Evolution of formularies Formulary systems have evolved over time.
Early formularies began as rudimentary drug lists developed by the military as early as the Revolutionary
War and came into more widespread use during the 1950s.9 Pharmacists, in conjunction with their
organizations, developed policies to dispense generic equivalent drugs when a specific brand-name drug
was prescribed. In the late 1950s, the ASHP minimum standard for pharmacies in hospitals called for the
implementation of a formulary system.10 During the 1960s, the concept of a hospital formulary
continued to grow. Hospitals developed policies that authorized pharmacists to make generic
interchanges in an institutional formulary system based on prior consent from physicians.11 ASHP and
the American Hospital Association (AHA) issued joint statements on the legality of formularies.12,13 The
American Medical Association (AMA) and the American Pharmaceutical (later Pharmacists) Association
(APhA) subsequently joined with ASHP and AHA to revise the statements.14 In 1965, two significant
events occurred: (1) Medicare listed formularies as a reimbursement eligibility requirement15 and (2)
the Joint Commission on the Accreditation of Hospitals (now known as the Joint Commission) included
an active P&T committee in its accreditation requirements.16 Even with these actions, formularies were
typically no more than lists of drugs stocked by the ASHP Guidelines on the P&T Committee and the
Formulary System (pre-press) 4 pharmacy. By the 1980s, literature describing the clinical and economic
value of well-designed formularies emerged. Evidence from the hospital setting was published first, soon
followed by evidence from the ambulatory care environment.11 This literature led to more widespread
acceptance of formularies by providers, payers, and industry. 5,17 Today, formulary systems are
considered an essential tool for healthcare organizations to foster interprofessional efforts to promote
the rational use of medications. Formularies have grown from simple drug lists to comprehensive
systems of medication-use policies intended to ensure safe, appropriate, and cost-effective use of
pharmaceuticals in patient care.18 P&T committee The P&T committee is generally the medical staff
committee responsible for managing the formulary system. The P&T committee provides an evaluative,
educational, and advisory service to the medical staff and organizational administration in all matters
pertaining to the use of available medications. The P&T committee should be responsible for overseeing
policies and procedures related to all aspects of medication use within an institution. The P&T
committee’s organization and authority should be outlined in the organization’s medical staff bylaws,
medical staff rules and regulations, and other organizational policies, as appropriate. The description of
organization and authority becomes even more important as healthcare facilities merge into larger
health systems. Typically, P&T committee member appointments and voting rights are made based on
ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 5 guidance from the
medical staff and other affected stakeholders. Voting members may include facility medical staff, other
prescribers, pharmacists, nurses, and administrators, and are a representative sample of the
organization. If the scope of the P&T committee includes a health system, site representation needs to
be addressed to ensure equitable input and voting authority from each facility. Additional supporting
P&T committee members may include quality improvement managers, medication safety leaders,
informaticists, other healthcare professionals and staff who participate in the medication-use process,
and patient and family engagement advisors. The P&T committee should have the following
administrative components in place to maximize meeting effectiveness: • Charter • Role of the P&T
secretary and/or formulary manager • Committee and subcommittee(s) responsibility and scope •
Process to track attendance • Definition of quorum • Process to allow (or disallow) delegation of vote •
Process to appeal committee decisions • Defined term limits for members • Process for identifying,
disclosing, addressing, and reporting conflicts of interest (COI) • Policy and procedures • Approach to
voting, including roll call votes to ensure transparency • Scope of committee responsibility (e.g., specific
site or entire system; inpatient or ASHP Guidelines on the P&T Committee and the Formulary System
(pre-press) 6 outpatient sites; drugs, devices, and biologics) • Process for managing minutes, agendas,
record keeping, and communication of decisions made Other responsibilities of the P&T committee
include medication-use evaluation (MUE), adverse drug event monitoring and reporting, medication
error prevention, medication safety, and development of clinical care plans and medication
management initiatives (e.g., delegation and practice protocols, restrictions, guidelines and clinical
pathways). Information about these activities is available in ASHP guidelines on the topics.19–22
Oversight of a formulary system and the capacity to make appropriate formulary decisions requires
consideration of patient care factors and a thorough, unbiased review of the biomedical literature.
Voting members should be required to provide COI statements to avoid actual or perceived interference
with evidence-based decisions.23 Some healthcare organizations exclude heathcare professionals with
COIs from P&T committee membership, whereas others allow participation in committee discussions but
prohibit voting on particular items. Practitioners requesting additions or changes to the formulary
should also be required to disclose financial relationships with pharmaceutical companies, payers and
insurance companies, and other potential COIs to the P&T committee. Management of COI should be
specified in organizational policies and procedures. Managing the formulary system Health systems
should develop, maintain, and implement a formulary management process. ASHP Guidelines on the
P&T Committee and the Formulary System (pre-press) 7 This evidence-based process should not be
based solely on economic factors. The formulary system should have aspects of financial stewardship
incorporated and be standardized within integrated health systems when standardization leads to
improved patient outcomes, safety, and cost effectiveness. Decisions on the management of a formulary
system should be founded on the evidence-based clinical, ethical, legal, social, logistical, philosophical,
quality-of-life, safety, and economic factors that result in optimal patient care.24-26 The process must
include the active and direct involvement of physicians, pharmacists, and other appropriate healthcare
professionals, as well representatives with expertise in finance, law, and informatics. Management of a
formulary system is a significant component of a healthcare organization’s ongoing medication-use
policy development process. A comprehensive, wellmaintained formulary is tailored to the
organization’s patient care needs, policy framework, and medication-use systems while ensuring
alignment with medication management standards of accrediting organizations.27 A well-managed
formulary system ensures a close relationship among the organization’s medication-use policies, the
therapies offered by the organization, and the medications routinely stocked in the pharmacy. A
formulary also identifies those medications that are most medically appropriate and cost-effective to
best serve the health interests of the health system’s patient population. The P&T Committee should
review all medications (see Appendix A) used in the health system. These may include alternative
remedies (herbals and supplements), nonprescription drugs, blood derivatives, contrast media, and
other diagnostic and treatment agents. 27 Institutional policies may need to be created for P&T
committee evaluation of agents not approved by the FDA (e.g., herbal supplements). The formulary
system should review and approve all policies related to the medication- ASHP Guidelines on the P&T
Committee and the Formulary System (pre-press) 8 use process; all medication-use policies, regardless
of their origination, should flow through the P&T committee. The organization’s medical staff leadership
(i.e., the body to which the P&T committee reports) should complete the final policy approval. Policy
review and revision should occur as new information becomes available and at regularly established
intervals (e.g., annually). The organization should have medication-use policies that address the
following: • How medications are requested for addition to or deletion from the formulary. • How
medications are reviewed for addition to or deletion from the formulary, including who performs the
reviews. • How and when drug class reviews are conducted. • The process for developing,
implementing, and monitoring medication-use guidelines. • Methods and policies for ensuring the safe
procurement, prescribing, distribution, administration, and monitoring of medications. • Methods for
selection of suitable manufacturers for specific medications (i.e., the pharmacy department is
responsible for specifications for the quality, quantity, and source of supply of all medications,
chemicals, biologicals, and pharmaceutical preparations used in the diagnosis and treatment of
patients). 28 • The process for using nonformulary agents within the hospital and health system. • The
process for managing radiopharmaceuticals. • The process for managing drug product shortages. • The
process for developing an organization or health system-specific MUE plan. • Policies regarding specific
medication-use processes (e.g., procurement, prescribing, distribution, administration, monitoring,
automation, and technology). ASHP Guidelines on the P&T Committee and the Formulary System (pre-
press) 9 • The process for disseminating medication-use policies and how users will be educated
regarding the process. • Process for accountability over medication delivery devices (e.g., infusion
pumps, dose error reduction software, intranasal atomizers). • Consideration of medication access
through prior authorization processes and patient assistance programs. • Implementation of P&T
committee decisions into the electronic health record (EHR). A formal process to review medication-use
policies should be in place. This process may include the use of expert panels or subcommittees of the
P&T committee. Expert panels or subcommittees should serve in an advisory role to the P&T committee,
and their membership should include recognized experts in their areas of practice. The P&T committee
may also find subcommittees that address specific therapeutic areas to be beneficial (e.g., pediatrics,
antimicrobial, oncology therapy, cardiovascular, adverse drug reaction, pharmacogenomics, or
biotechnology subcommittees). Panels and subcommittees are helpful in applying clinical study results
to specific patient populations and developing recommended strategies for the safe and effective use of
medications. Subcommittee and panel members can help educate groups of clinicians, who ultimately
drive prescribing behaviors, about significant formulary changes. User groups, representing those
primarily affected by the policy, may also be helpful. The P&T committee should have formal
interactions (i.e., communication lines) with other committees whose functions may affect the
medication-use process. These committees would include those responsible for developing tools to
facilitate medication use (e.g., forms ASHP Guidelines on the P&T Committee and the Formulary System
(pre-press) 10 or order set review committee, computerized provider order entry committee), those
concerned with safety or performance improvement (e.g., quality improvement or patient safety
committees), those involved in developing patient care policies (e.g., medical and nursing committees),
those involved with investigational medications (e.g., investigational review boards), and other
committees whose actions may affect medication use (e.g., nutrition, equipment and supply, finance
committees, or patient and family engagement advisors). Recommendations from other committees,
subcommittees of P&T, expert panels, and others should be submitted to the P&T committee for review.
P&T committee decisions on recommendations should be communicated to the recommending group in
a timely fashion. Finally, the role of pharmaceutical company representatives and medical science
liaisons in a healthcare organization should be carefully considered. Organizational guidelines should
define appropriate relationships and interactions with such individuals. At a minimum, these guidelines
should address the provision of pharmaceutical samples, indirect or direct funding support, and
educational programming regarding formulary and nonformulary medications. Applications for
formulary additions should be initiated and completed independently by the requesting healthcare
provider and not by an industry representative or vendor. Refer to ASHP’s Guidelines on Pharmacists’
Relationships with Industry for more information on appropriate interactions with industry.29
Evaluating medications for inclusion in the formulary The P&T committee should use a structured,
evidence-based process in the evaluation of ASHP Guidelines on the P&T Committee and the Formulary
System (pre-press) 11 medications for formulary consideration. The P&T committee should be provided
with information that reflects a thorough, accurate, and unbiased review and analysis of the evidence
available in the scientific literature. The evaluation process should encourage objective consideration of
clinical and care delivery information, facilitate communication, foster positive patient outcomes, and
support safe and effective medication ordering, dispensing, administration, and monitoring. Decisions
made by the P&T committee should support improved patient care outcomes across the continuum of
care, including considerations regarding patient access to medications upon discharge. Evidence-based
evaluation. Evidence-based medicine is a systematic approach to the evaluation of biomedical literature
and application to clinical practice and should be applied to formulary decision-making for medication
product selection.25 Evidence-based decision-making standardizes and improves the quality of patient
care and promotes cost-effective prescribing.25,26 To practice evidence-based medicine, practitioners
must be proficient in retrieving, evaluating, and applying the biomedical literature to clinical practice.
Inclusion of a medication on a health system’s formulary or the adoption of a medication-use guideline
should reflect an evidence-based evaluation. Evidence-based decision-making incorporates the
systematic approach to reviewing, evaluating, and applying the biomedical literature to guide formulary
decisions. Various types and strengths of evidence (e.g., randomized clinical trials, meta-analyses, case
reports, association consensus statements) may be useful in the decision-making process. Although
different types of evidence are available for application, those with stronger evidence should be used to
drive formulary decisions (e.g., meta-analyses, randomized controlled trials). Other ASHP Guidelines on
the P&T Committee and the Formulary System (pre-press) 12 types of evidence have a role in the
decision-making process, however, and may be appropriate when stronger evidence is not available.
Observational studies (i.e., case–control and cohort studies), case reports, and consensus opinions may
be valuable even when stronger evidence is available. Some organizations find it useful to grade
evidence when evaluating formulary requests; several tools are available for this purpose.30–34
Published evidence and expert opinion are not the only resources available to aid in the formulary
decision-making process. Internal data and prescribing and outcomes information may be helpful in
formulary decision-making. When published data are not available, it may be appropriate to incorporate
expert opinion into the review process. Experts in practice areas sometimes have access to unpublished
data or reports that may offer insight into difficult formulary decisions. The formulary decision-making
process should be guided by an independent review of evidence published in the biomedical literature,
application of expert opinion, and use of internal data and benchmarking programs (see Appendix B for
a description of the four major types of reviews used in such evaluations). If a P&T committee uses
medication dossiers prepared by a pharmaceutical manufacturer, it should do so with the utmost
caution, since the objectivity of these documents may be challenged. Information used in the formulary
decision-making process should be provided to the P&T committee in a written document with a
standard format (e.g., a drug monograph, drug review, drug-evaluation document).35 All information
provided in the drug-evaluation document should be referenced to the evidence or identified as a
conclusion supported by evidence. Any areas of consensus recommendations or opinion should be
clearly identified. ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 13
Formulary status recommendations (e.g., from drug information services or expert groups) may be
included in the drug-evaluation document. Recommendations should consider the formulary status
(addition or rejection) of a medication, as well as the need for restrictions, educational efforts, or
policies and procedures to ensure safe and appropriate use within the health system.
Pharmacoeconomic assessments. Rigorous pharmacoeconomic evaluations can and should be
conducted in some cases when reviewing new medications. These evaluations should explicitly state the
perspective of the analysis (e.g., patient, healthcare provider, payer) and should include consideration of
all costs and consequences relevant to that perspective. When new medications being considered are
found to be therapeutically equivalent to existing alternatives (i.e., having equivalent efficacy and
safety), then the cost-minimization approach is appropriate. In these circumstances, it is important to
consider costs associated with the medication and non-medication-related costs (e.g., costs of
administration, monitoring, prolonged hospital stay, operational costs, and laboratory test monitoring;
costs to patients and providers). While cost-effectiveness analysis (evaluating the incremental difference
in investment necessary to produce an incremental difference in clinical outcome) is another potentially
useful analytic approach, it is not often used for formulary decision-making because of its complexity
and need for strong evidence or data. The academic value of this approach lies in its ability to show how
little (or how much) must be spent to achieve a particular margin of clinical advantage when comparing
an alternative that is more expensive but safer or more efficacious. No standards currently exist to
determine what cost is reasonable for a given ASHP Guidelines on the P&T Committee and the
Formulary System (pre-press) 14 improvement in outcome; however, it is unreasonable to recommend
alternatives of lower quality simply to achieve cost savings. This approach can be used to demonstrate
how a decrease in clinical outcomes associated with the use of a less-expensive agent can be offset by
investing the savings achieved in other interventions that produce even greater total benefits. When
evaluating cost-effectiveness, it is important to consider the site of care for administration of the drug.
Cost-utility evaluations (evaluating the incremental difference in investment necessary to produce an
incremental difference in quality-of-life-adjusted clinical outcome [e.g., incremental cost per quality-
adjusted life years gained for one medication versus another]) may also be beneficial by serving to
reflect patient preference in formulary decision-making. However, the same concerns related to the use
of cost-effectiveness evaluations apply to this approach.36–38 Decision analysis models incorporating
local data can be employed when published pharmacoeconomic data are limited or unavailable.
Probabilities for each outcome can be extracted from the published literature or drawn from local data
sources, which would provide a more relevant local perspective on outcomes. Costs associated with
medications and outcomes should reflect those of the healthcare system. Pharmacoeconomic analyses
published in the medical literature or provided in the manufacturer’s formulary dossier should be
analyzed carefully before being included as part of the review process. Particular attention should be
paid to the assumptions made in these studies. In many situations, assumptions made to simplify
economic studies are not valid in particular institutions. Institution-specific costs are often different from
the costs used in ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 15
published studies, and local data should be used when incorporating their results into medication
reviews.39,40 Even if a formal pharmacoeconomic evaluation is not included in a drug review
document, a financial evaluation must be conducted, including consideration of site of care, non-
medication-related costs, and financial consequences to the pharmacy and to the organization as a
whole. Formulary exceptions. Exclusion of a medication from a formulary may affect coverage of and
access to the medication. In a closed formulary system, for example, only medications listed on the
formulary are covered under the patient’s drug benefit. Regardless of healthsystem setting, the
formulary system should include an exception process that provides prescribers and patients with timely
access to medications that are not on the formulary but are medically necessary for the care of the
patient. The underlying principle for such a process is that unique patient needs may not be satisfied by
use of the formulary medications. The formulary exception process should generate information on
nonformulary medication use that will enable the P&T committee to evaluate trends in such use. Criteria
for approval of nonformulary medications should be developed (e.g., allergy to or therapeutic failure of
formulary alternative, condition not treatable by formulary medications) and guidelines for use should
be considered for nonformulary medications if they carry patient safety risks, have a Risk Evaluation and
Mitigation Strategy (REMS), are expensive, and require complicated preparation. Subformularies.
Depending on state regulations, subformularies may be developed and maintained, using the same
evidence-based process, to provide lists of appropriate and ASHP Guidelines on the P&T Committee and
the Formulary System (pre-press) 16 approved medications for furnishing by nonphysician providers or
to specific patient subsets, such as Medicare patients. Health systems must follow specific rules and
regulations provided under the U.S. Medicare Modernization Act of 2003 in their evaluation and
inclusion of medications in a Medicare formulary for those medications to be covered. 41 Strategies for
managing medication use Common strategies for managing medication use via the formulary include
use of generic drugs, biosimilars, and specialty medications; therapeutic interchange; guided-use
policies, clinical practice guidelines; and MUE. Generic drugs. Optimizing the number of medication
entities and products available from the pharmacy can produce substantial patient care and financial
benefits. These benefits are greatly increased through the use of generic equivalents (drugs considered
bioequivalent by FDA [i.e., AB-rated drug products42]). The use of generic equivalents is encouraged in
order to provide the best possible care at an affordable cost. Use of generic drugs that have been
deemed bioequivalent by FDA does not require review or approval by the P&T committee, although a
review of all new generic medications for key safety issues (e.g., look-alike, soundalike concerns) should
be conducted to prevent medication errors when possible. For some drug categories, such as those with
a narrow therapeutic range, a more thorough evaluation of the bioequivalency data and approval of
experts or the P&T committee should be considered before implementing a generic substitution. The
P&T committee should establish policies and procedures governing the dispensing of generic
equivalents when branded products are ordered. These policies and procedures ASHP Guidelines on the
P&T Committee and the Formulary System (pre-press) 17 should include the following points: • The
pharmacist is responsible for selecting from available generic equivalents those drugs to be dispensed
pursuant to a prescriber’s order for a particular medication. • The prescriber has the option, at the time
of prescribing, to specify the brand or supplier of the drug to be dispensed for that particular medication
order if considered clinically justified. • The prescriber’s decision should be based on pharmacologic or
therapeutic considerations (or both) relative to that patient. Biosimilars. A biosimilar is a biological
product that is highly similar to and has no clinically meaningful differences from an existing FDA-
approved reference product.43 Several entities have been approved as biosimilars by the FDA, and
inclusion of these products on formulary should be considered as a strategy for management of the
medication-use system. Biosimilars are not generically equivalent to the reference product, so the P&T
committee should be involved in the decision to include these products on formulary. The implications
for patients must also be considered, including legal and regulatory restrictions, coverage and
reimbursement models by payers, differences in clinical indications or activity between the reference
product and the biosimilar, and contractual obligations. There are several considerations when
evaluating biosimilars. When there are multiple biosimilars available for the same reference product, a
close review of indications for each of the biosimilars should occur, as the indications that each
biosimilar have may differ compared to each other and the reference product. The FDA can deem a
biosimilar as interchangeable, however, even if a product does not have this status noted in its labelling.
Available switching ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 18
data should be reviewed closely to determine whether patients currently receiving treatment with the
reference product can be switched to the biosimilar. In instances in which the FDA has determined a
biosimilar product to be interchangeable, state regulations should be reviewed to determine actions
required by the pharmacist when dispensing a biosimilar with an interchangeable status. In instances in
which an institution may elect to have both a reference product and a biosimilar on formulary, careful
attention should be paid to how these are built in the EHR to ensure the appropriate product is utilized.
Therapeutic interchange. Therapeutic interchange is the authorized exchange of therapeutic alternatives
in accordance with previously established and approved written guidelines, policies, or protocols within
a formulary system.1,44 Drugs appropriate for therapeutic interchange are drug products with different
chemical structures that are expected to have similar therapeutic effects and safety profiles when
administered to patients in therapeutically equivalent doses. Therapeutic interchange provides
pharmacists with the authorization to use a formulary therapeutic alternative in place of a nonformulary
medication or a nonpreferred formulary medication without having to contact the prescriber. Ideally,
therapeutic interchanges are built into the EHR to allow for seamless substitution of formulary products.
A process should be established for when the prescriber wishes to opt out of the interchange. Adequate
educational initiatives should be undertaken to ensure that everyone affected (prescribers, patients,
pharmacists, nurses, and other healthcare professionals) is notified of the therapeutic interchange.
Guided-use strategies. Medications may be added to the formulary with additional processes in place to
guide the use of the medications to improve therapeutic outcomes, ASHP Guidelines on the P&T
Committee and the Formulary System (pre-press) 19 prevent adverse events, or reduce costs. All
guidelines for use for both on- and off-label indications should be developed using evidence-based
decisions, based on the current medical literature. 45 Examples of strategies to help guide the use of
medications may include the following. Established-use criteria. Patients must meet the established
criteria before the medication is dispensed. A process should be developed to cover situations in which
the patient does not meet the established criteria, but the medication is nevertheless determined to be
medically necessary. This strategy may also be useful when medications are in short supply. Restricting
drug use by specialty service. A specific service must approve the use of the drug before dispensing. This
strategy can be used when inappropriate use or severe adverse effects may occur, and it can also be
employed for antimicrobial agents when inappropriate use or overuse can result in resistant organisms
and pose a danger to the general patient population or the public. Alternatively, ordering of a specific
medication may be limited to a specific group of prescribers (e.g., restricting use of chemotherapy
agents to oncologists). Designating medications for use in specific areas. Such policies can be helpful
when administration of a medication requires special equipment or staff with particular skills to use the
medication safely (e.g., limiting neuromuscular blockers to operating rooms and critical care areas).
Approval of medical director (or designee) before drug use. This strategy is particularly appropriate
when the P&T committee has reviewed a high-cost medication and determined that the drug has little
or no role in the care of patients at that organization but a prescriber would like to use the medication
on a nonformulary basis. This strategy may also be used as an ASHP Guidelines on the P&T Committee
and the Formulary System (pre-press) 20 approval pathway for medications requested for use outside of
established criteria outlined in the formulary. Clinical practice guidelines. Clinical practice guidelines are
developed and disseminated by national and international organizations, but they can also be developed
locally. Whether the medication formulary is a reflection of existing clinical practice guidelines in a
particular organization or vice versa, it is critical that the guidelines and formulary are consistent. If a
specific medication is recommended by a clinical practice guideline, it should in the majority of cases be
on the formulary. As formulary changes are made, agents may need to be removed from or replaced in
existing guidelines. Guidelines should avoid recommending use of nonformulary medications, and they
can be useful in discouraging nonformulary medication use and guiding the appropriate use of formulary
products when necessary. Guidelines are frequently developed to address complex or particularly
expensive medication therapies. However, complicated specialty therapies that will affect the care of
very few patients may not justify the time and resources necessary to develop and maintain a guideline.
Guidelines may be medication specific or disease oriented and may overlap in their scope of coverage.
The development of a clinical practice guideline should begin with the synthesis of all available
biomedical evidence addressing the guideline topic. In many cases, guidelines from other organizations,
both national and local, can be used as a starting point for development. The subsequent consensus
process, eliciting feedback and input from local stakeholders, is critical. Data from the organization
should be used to make informed decisions during the consensus process. After the consensus process is
completed, the guideline should be reviewed ASHP Guidelines on the P&T Committee and the Formulary
System (pre-press) 21 and approved by the P&T committee. The dissemination and implementation of
guidelines in the practice environment must also be carefully executed. Communication about the
availability of guidelines is necessary. Guidelines should be readily available through existing health-
system platforms. If feasible, it is recommended to build the guidelines into the computerized provider
order entry system (e.g., through order set creation) to facilitate the appropriate care of the patient.
Every guideline should include a time frame for future review and revision. If utilization of a medication
is being requested outside established health-system guidelines for appropriate use, scientific evidence
to support safety and efficacy should be provided and reviewed to substantiate the request. Specialty
medications. P&T committees should be involved in the organization’s approach to managing specialty
medications to ensure the pharmacy has the ability to provide medications in a timely manner, to
support patient access to medications, and provide continuity of care. ASHP has resources to aid in
specialty pharmacy management, including the ASHP Specialty Pharmacy Resource Guide.46 This guide
provides guidance on dispensing the medication directly to the site of care for patient administration
(white bagging) or to the patient, who then carries it to the site of care for administration (brown
bagging). Another strategy to consider in management of specialty pharmaceuticals is clear bagging.
Clear bagging is the delivery of a patient-specific specialty pharmaceutical directly from a health
system’s specialty pharmacy directly to the health-system site of service, where it is then administered.
47 MUE process. MUE is a quality-improvement activity, but it can also be considered a ASHP Guidelines
on the P&T Committee and the Formulary System (pre-press) 22 formulary system management
technique. MUEs have traditionally involved evaluating evidence-based criteria to determine the health
system’s compliance with established standards. Interventions could then be used to improve any
aspect of the medication use process based on MUE data analyses. MUE can be simply informative
(collecting data to guide decision-making) or used to measure the effect of interventions, such as the
addition of a new agent to the formulary or the implementation of a new medication-use policy. While
MUE often focuses on problem-prone, high-risk, or high-cost medications, MUE can be used to examine
any aspect of medication use that is problematic to the institution conducting the evaluation.
Medications recently added to the formulary should be evaluated, especially if there is the potential for
inappropriate use or adverse effects. This review should occur 6–12 months after their addition to the
formulary. High-cost, high-use, or problem-prone medications and outcomes of specific disease states
are also good candidates for evaluation. A systematic plan to monitor, evaluate, and improve
medication use should be established within the organization.19 Such a plan is an accreditation
requirement for many organizations (e.g., Joint Commission27). The P&T committee, or its equivalent,
should be involved in the MUE process. Refer to ASHP’s Guidelines on Medication Use Evaluation for
more detailed information conducting an MUE.19 Incorporating patient safety issues in the decision-
making process The P&T committee should systematically address medication and patient safety issues
as part of its deliberations. The P&T committee should ensure that medication-use policies adequately
ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 23 address potential risk
and safety issues. Hospital or health-system medication-event data, including near misses, should
consistently be reviewed by the P&T committee, along with recommendations to prevent future events.
The P&T committee should also review available information on medication or patient safety events
reported by other organizations to identify ways to prevent medication events and disseminate the
information to healthcare providers and, when appropriate, patients. When evaluating a medication for
inclusion on the formulary, the P&T committee and its supporting subcommittees or panels should
consider adverse effects, preparation issues, sound-alike or look-alike potential, practitioner safety, and
dosing or administration issues. If a product has a REMS program, the requirements of this program
should be carefully reviewed to ensure the institution can meet the requirements. When implementing
formulary decisions for medications that have REMS, there should be processes in place to ensure
compliance both during implementation and on an ongoing basis. Proactive assessments should be
conducted to identify potential safety concerns posed by use of the medication, and proposed strategies
to mitigate those risks should be implemented by the P&T committee. In addition, quality improvement
projects to improve the safety of specific medications or to evaluate the processes involved should be
conducted and reviewed by the P&T committee. The P&T committee should champion evidence-based
fail-safe techniques (e.g., bar-coding) to prevent medication events. Resources that provide information
on medication or patient safety events include the Institute for Safe Medication Practices
(www.ismp.org) and Medwatch. The Joint Commission, Institute for Healthcare Improvement, and
National Center on Patient Safety provide ASHP Guidelines on the P&T Committee and the Formulary
System (pre-press) 24 information about conducting and examples of failure mode and effects analysis
(FMEA) projects on their websites (www.jointcommission.org/, www.ihi.org/, and
www.patientsafety.va.gov). Implementation of formulary decisions into the EHR Use of the EHR to
implement, guide, and evaluate decisions made by the P&T Committee is essential. EHR technology
functionality should be maximized to support drug policy and formulary management decisions. The
EHR should provide guidance on dosing, monitoring, and restrictions/limitations at the point of
prescription and verification. A standard process, including established expectations for timeliness,
should be developed to consistently and efficiently implement these decisions into the EHR. Multi-
hospital systems and integrated delivery networks that share the same EHR platform and formulary
review process should centralize the coordination of implementation.48 EHR implementation efforts
should be coordinated with operational changes and education requirements identified in the
decisionmaking process. Finally, resources and personnel available to support implementation into the
EHR should interface with the P&T committee to ensure understanding and shared expectations of the
EHR technology functionality. In addition, key content experts charged with evaluating and proposing
drug policy and formulary management decisions should collaborate with informatics personnel on the
design and validation of EHR content. Drug product shortages Health systems frequently need to
address drug product shortages. Drug product shortages ASHP Guidelines on the P&T Committee and
the Formulary System (pre-press) 25 disrupt patient care and impact all aspects of the medication-use
system, including purchasing, storage, automation systems, the EHR, preparation, administration,
monitoring, and education. During a drug product shortage, the P&T committee plays an important role.
The P&T committee needs to develop strategies to address shortages in a timely manner, including
designating appropriate therapeutic alternatives, identifying strategies for mitigating use of available
drug product, and establishing use restrictions. All of these strategies should be developed based on
available literature and best practices. Therapeutic interchange can be useful in dealing with critical drug
product shortages. The P&T committee should work collaboratively with other committees and
departments, such as specific medical departments, nursing, and risk management (when necessary) to
develop effective management plans for addressing shortages. Given the dynamic nature of drug
shortages, it is not always possible to obtain approval from P&T committee members prior to
implementation of strategies if there is a need for urgent changes. To make sure the P&T committee is
aware of all changes related to drug shortages, organizations should include a drug shortage update as a
regular agenda item for the P&T committee. Communication with patients and staff is crucial to
effectively manage shortages. Effective integration of these strategies into the EHR is key to successful
implementation of a drug shortage plan. Various strategies exist for communication in the EHR,
including placing electronic alerts on medications, blocking the ordering of medications on shortage, and
facilitating the build of new medication records or order sets to guide use of alternative agents during
the time of the shortage. More information about managing drug product shortages can be found in the
ASHP ASHP Guidelines on the P&T Committee and the Formulary System (pre-press) 26 Guidelines on
Managing Drug Product Shortages.49 Implementing medication-use policies Various tools can be used
to implement medication-use policies. The policy should be integrated directly into the therapeutic
decision-making processes that guide the use of a medication during order entry or incorporated into
diagnosis-specific electronic treatment plan. Other specific ways of communicating information about a
medication-use policy may include the use of • Inservice education, • Facility-approved social media, •
Grand rounds, • Communication between pharmacists and prescribers • Staff meetings, • E-mail, •
Electronic newsletters, • Prescriber detailing, and • Pharmacy or institutional websites. Outcome-driven
projects may be beneficial in illustrating the value of a new medication-use policy and support further
expansion. Reimbursement strategies and considerations New payment models require that P&T
committee members are astute in their understanding ASHP Guidelines on the P&T Committee and the
Formulary System (pre-press) 27 of the hospital and health system’s payment policies and
reimbursement strategies related to medications. A balanced approach to managing a hybrid
reimbursement structure between traditional fee-for-service models and emerging value-based
contracts will be required. Financing and reimbursement for medications is complex; hospitals and
health systems can no longer exclusively focus on manufacturing contracts, wholesaler agreements, and
inpatient reimbursement. Large health systems and integrated systems must consider implications of
medication reimbursement by Medicare, Medicaid, commercial, and private payers. If applicable, 340B
policies must also be considered. Prior to approval of high-cost drugs, in collaboration with the finance
department, there should be a benefits investigation conducted, factoring in local payer mix, plans for
financial monitoring, and payer negotiations. The organization should have a defined process and
responsible department for validating reimbursement of therapy and financial outcomes over time.
Factors include site of care decisions in determining where a medication will be administered. Each
organization should have policies on the use of medications not directly procured by the hospital
pharmacy. For example, some specialty medication payer agreements circumvent traditional buy-and-
bill dispensing channels and instead use white or brown bagging strategies. 47 Furthermore, patient
access to medications upon discharge or during transitions of care between care settings needs to be
evaluated and systems need to be in place to ensure continuity of medication use and to decrease the
potential to prolong length of stay due to medications initiated during an inpatient stay that may be
restricted elsewhere. Conclusion ASHP Guidelines on the P&T Committee and the Formulary System
(pre-press) 28 A formulary system is the multidisciplinary, evidence-based process employed by an
organization to select and use medications that offer the best therapeutic outcomes while minimizing
potential risks and costs for patients. Organizations should employ the MUE process to continually
improve how medications are used within the organization at all steps in the medication-use process.
Medication use is an inherently complex process that requires constant evaluation. Organizations need
to implement all necessary tools and processes to meet the goals of safe and effective medication use.
Professionals involved in the medicationuse process need to know and understand how the
organization’s medication-use policies and processes can be incorporated into their daily work to ensure
medications are used appropriately and safely. Technology offers many opportunities to make those
processes more effective and efficient. Communicating the actions related to medication use is a
constant challenge that organizations need to address.

Acknowledgments ASHP gratefully acknowledges the following organizations and individuals for
reviewing these guidelines (review does not imply endorsement): American Pharmacists Association
(APhA); Maryland Society of Health System Pharmacists (MSHP); Thomas S. Achey, Pharm.D., M.S.,
BCPS; Ryan C. Costantino, Pharm.D., M.A., BCPS, BCGP; Katie Foster, Pharm.D., M.S., FCCM; Rena
Gosser, Pharm.D., BCPS; Kathleen M. Gura, Pharm.D., BCNSP, FASHP; Charzetta H. James, Pharm.D.,
CPh., M.B.A., M.H.A., FACHE, PRS; Isha John, Pharm.D., M.B.A. (APhA); Indrani Kar, Pharm.D.; Nicole
Kiehle, Pharm.D., BCPS (MSHP); Eric C. Kutscher, Pharm.D., MBA, FASHP; Patrick M. Malone, Pharm.D.,
FASHP; Nancy MacDonald, Pharm.D., BCPS, FASHP; Kathryn Clark McKinney, Pharm.D., M.S., BCPS,
FACHE, FASHP; Valerie Dee Nolt, Pharm.D., BCPPS; James Ponto, M.S., BCNP, FASHP; Preetham Talari,
M.D., FACP, SFHM; Philip J. Trapskin, Pharm.D., BCPS; Tyler A. Vest, Pharm.D., M.S., BCPS; Geralyn
Waters, Pharm.D., BCPS; Jody Jacobson Wedret, R.Ph., FASHP, FCSHP. ASHP also gratefully
acknowledges the contributions of authors of previous versions of these guidelines: Linda S. Tyler,
Pharm.D., FASHP; Mirta Millares, Pharm.D., FCSHP, FASHP; Andrew L. Wilson, Pharm.D., FASHP; Lee C.
Vermeulen, Jr., B.S.Pharm., M.S.; J. Russell ASHP Guidelines on the P&T Committee and the Formulary
System (pre-press) 29 (Rusty) May, Pharm.D., FASHP; Michael A. Valentino, R.Ph. MHSA; and Sabrina W.
Cole, Pharm.D.

Disclosures The authors have declared no potential conflicts of interest. Additional information
Developed through the ASHP Council on Pharmacy Practice and approved by the ASHP Board of
Directors on November 16, 2020. These guidelines supersede the ASHP Guidelines on the Pharmacy and
Therapeutics Committee and the Formulary System dated January 28, 2008, and the ASHP Statement on
the Pharmacy and Therapeutics Committee and the Formulary System dated June 10, 2008. References
1. Principles of a sound drug formulary system. In: Hawkins B, ed. Best practices for hospital and health-
system pharmacy: positions and guidance documents of ASHP. Bethesda, MD: American Society of
Health-System Pharmacists; 2018:233–6.

2. American Heart Association Policy Statement on Drug Formularies (2018).

https://www.heart.org/-/media/files/about-us/policy-research/preventionnutrition/drug-formulary-
statement-2018.pdf (accessed 2020 Oct 14).
3. American College of Physicians. Position Paper: Therapeutic Substitution and Formulary Systems
(1990). https://www.acponline.org/acp_policy/policies/therapeutic_substitution_formulary_s
ystems_1990.pdf (accessed 2020 Oct 14).

4. Laing R, Tisocki K. How to develop a national formulary based on the WHO model formulary (2004).
http://archives.who.int/EMLib/docs/National_MF_Manual2004- 8.pdf (accessed 2020 Oct 14).

5. American Medical Association. Policy H-125.991: drug formularies and therapeutic interchange.
https://policysearch.amaassn.org/policyfinder/detail/formulary?uri=%2FAMADoc%2FHOD.xml-0-
227.xml (accessed 2020 Oct 14).

6. American Medical Association. Policy H-285.965: managed care cost containment involving
prescription drugs. https://policysearch.amaassn.org/policyfinder/detail/drug%20formularies%20?uri=
%2FAMADoc%2FHOD.xml-0- 2089.xml (accessed 2020 Oct 14).

7. Academy of Managed Care Pharmacy. AMCP format for formulary submissions.

http://www.amcp.org/practice-resources/amcp-format-formulary-submissions/ (accessed 2019 Jun 3).
8. American Academy of Family Physicians. Patient-centered formularies.
https://www.aafp.org/about/policies/all/patient-formularies.html (accessed 2020 Oct 14).

9. Balu S, O’Connor P, Vogenberg FR. Contemporary issues affecting P&T committees. Part 1: The
evolution. P&T. 2004;29:709–11 ASHP Guidelines on the P&T Committee and the Formulary System
(pre-press) 30

10. American Society of Hospital Pharmacists. Minimum standard for pharmacies in hospitals. Am J Hosp
Pharm. 1958; 15:992–4.
(HOSPITAL MANAGEMENT MANUAL OF DOH CHAP 6)
DRUG PROCUREMENT

ANNEX 9: GUIDE TO GOOD STORAGE PRACTTICES FOR PHARMACEUTICALS, WHO

1. Introduction This guide is intended for those involved in the storage, transportation and
distribution of pharmaceuticals. It is closely linked to other existing guides recommended by the
WHO Expert Committee on Specifications for Pharmaceutical Preparations, such as:
• Good trade and distribution practice (GTDP) of pharmaceutical starting materials (1);
• The stability testing of pharmaceutical products containing well-established drug substances in
conventional dosage forms (information given in connection with regulation for marketing
authorization) (2);
• Good manufacturing practices (GMP) (3); 1 This guidance has been prepared in close
collaboration with the International Pharmaceutical Federation (FIP). 126
• The cold chain, especially for vaccines and biologicals;
• The International Pharmacopoeia (4). The objective of this guide is to supplement the above-
mentioned documents by describing the special measures considered appropriate for the
storage and transportation of pharmaceuticals. However, they may be adapted to meet
individual needs where necessary, provided that the desired standards of quality are still
achieved. The guidelines are applicable not only to manufacturers of medicinal products but also
to pharmaceutical importers, contractors and wholesalers, and community and hospital
pharmacies. They should be adjusted in line with the type of activity where the storage of
pharmaceuticals is taking place. National or regional regulations should be followed for all
related activities.
2. Glossary The definitions given below of some of the terms used in this document take into
account the terminology of current regulations and recommendations. active pharmaceutical
ingredient (API) Any substance or mixture of substances intended to be used in the manufacture
of a pharmaceutical dosage form and that, when used in the production of a drug, becomes an
active ingredient of that drug. Such substances are intended to furnish pharmacological activity
or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to
affect the structure and function of the body.
Contamination- The undesired introduction of impurities of a chemical or microbiological
nature, or of foreign matter, into or onto a starting material, or intermediate or finished product
during production, sampling, packaging or repackaging, storage or transport.
cross-contamination- Contamination of a starting material, intermediate product or finished
product with another starting material or product during production.
Excipient- A substance, other than the active ingredient, which has been appropriately
evaluated for safety and is included in a drug delivery system to: 127 — aid in the processing of
the drug delivery system during its manufacture; — protect, support or enhance stability,
bioavailability, or patient acceptability; — assist in product identification; or — enhance any
other attribute of the overall safety and effectiveness of the drug during storage or use.
Expiry date- The date given on the individual container (usually on the label) of a drug product
up to and including which the product is expected to remain within specifications, if stored
correctly. It is established for each batch by adding the shelf-life to the date of manufacture.
Labelling -The action involving the selection of the correct label, with the required information,
followed by line clearance and application of the label.
 Manufacture -All operations of purchase of materials and products, production, quality control,
release, storage and distribution of finished products, and the related controls.
Material- A general term used to denote starting materials (active pharmaceutical ingredients
and excipients), reagents, solvents, process aids, intermediates, packaging materials and
labelling materials.
Packaging- material Any material, including printed material, employed in the packaging of a
pharmaceutical product, but excluding any outer packaging used for transportation or shipment.
Packaging materials are referred to as primary or secondary according to whether or not they
are intended to be in direct contact with the product.
pharmaceutical -product Any medicine intended for human use or veterinary product
administered to food-producing animals, presented in its finished dosage form or as a starting
material for use in such a dosage form, that is subject to control by pharmaceutical legislation in
both the exporting state and the importing state.
Production- All operations involved in the preparation of a pharmaceutical product, from receipt
of materials, through processing, packaging and repackaging, labelling and relabelling, to
completion of the finished product.
retest date- The date when a material should be re-examined to ensure that it is still suitable for
use.
storage -The storing of pharmaceutical products and materials up to their point of use.
supplier -A person providing pharmaceutical products and materials on request. Suppliers may
be agents, brokers, distributors, manufacturers or traders. Where possible, suppliers should be
authorized by a competent authority.
3. Personnel 3.1 At each storage site (e.g. that of a manufacturer, distributor, wholesaler,
community or hospital pharmacy) there should be an adequate number of qualified personnel
to achieve pharmaceutical quality assurance objectives. National regulations on qualifications
should be followed. 3.2 All personnel should receive proper training in relation to good storage
practice, regulations, procedures and safety. 3.3 All members of staff should be trained in, and
observe high levels of, personal hygiene and sanitation. 3.4 Personnel employed in storage areas
should wear suitable protective or working garments appropriate for the activities they perform.
4. Premises and facilities Storage areas 4.1 Precautions must be taken to prevent unauthorized
persons from entering storage areas.
4.2 Storage areas should be of sufficient capacity to allow the orderly storage of the various
categories of materials and products, namely starting and packaging materials,
intermediates, bulk and finished products, products in quarantine, and released, rejected,
returned or recalled products.
4.3 Storage areas should be designed or adapted to ensure good storage conditions. In
particular, they should be clean and dry and maintained within acceptable temperature
limits. Where special storage conditions are required on the label (e.g. temperature, relative
humidity), these should be provided, checked, monitored and recorded. Materials and
pharmaceutical products should be stored off the floor and suitably spaced to permit
cleaning and inspection. Pallets should be kept in a good state of cleanliness and repair.
4.4 Storage areas should be clean, and free from accumulated waste and vermin. A written
sanitation programme should be available indicating the frequency of cleaning and the
methods to be used to clean the premises and storage areas. There should also be a written
 programme for pest control. The pest-control agents used should be safe, and there should
be no risk of contamination of the materials and pharmaceutical products. There should be
appropriate procedures for the clean up of any spillage to ensure complete removal of any
risk of contamination.
4.5 Receiving and dispatch bays should protect materials and products from the weather.
Reception areas should be designed and equipped to allow containers of incoming materials
and pharmaceutical products to be cleaned, if necessary, before storage.
4.6 Where quarantine status is ensured by storage in separate areas, these areas must be
clearly marked and their access restricted to authorized personnel. Any system replacing
physical quarantine should provide equivalent security. For example, computerized systems
can be used, provided that they are validated to demonstrate security of access.
4.7 There should normally be a separate sampling area for starting materials in a controlled
environment. If sampling is performed in the storage area, it should be conducted in such a
way as to prevent contamination or cross-contamination. Adequate cleaning procedures
should be in place for the sampling areas.
4.8 Physical or other equivalent validated (e.g. electronic) segregation should be provided for
the storage of rejected, expired, recalled or returned materials or products. The materials or
products, and areas concerned should be appropriately identified.
4.9 Highly active and radioactive materials, narcotics and other hazardous, sensitive and/or
dangerous materials and pharmaceutical products, as well as substances presenting special
risks of abuse, fire or explosion, (e.g. combustible liquids and solids and pressurized 130
gases) should be stored in a dedicated area that is subject to appropriate additional safety
and security measures.
4.10 Materials and pharmaceutical products should be handled and distributed according to
GMP as defined in this document.
4.11 Materials and pharmaceutical products should be handled and stored in such a manner
as to prevent contamination, mix-ups and cross-contamination.
4.12 2 Materials and pharmaceutical products should be stored in conditions which assure
that their quality is maintained, and stock should be appropriately rotated. The “first
expired/first out” (FEFO) principle should be followed.
4.13 Rejected materials and pharmaceutical products should be identified and controlled
under a quarantine system designed to prevent their use until a final decision is taken on
their fate.
4.14 Narcotic drugs should be stored in compliance with international conventions, and
national laws and regulations on narcotics.
4.15 Broken or damaged items should be withdrawn from usable stock and separated.
4.16 Storage areas should provide adequate lighting to enable all operations to be carried
out accurately and safely.
4.17 Storage conditions for pharmaceutical products and materials should be in compliance
with the labelling, which is based on the results of stability testing (see Appendix).
4.18 Recorded temperature monitoring data should be available for review. The equipment
used for monitoring should be checked at suitable predetermined intervals and the results
of such checks should be recorded and retained. All monitoring records should be kept for at
least the shelf-life of the stored material or product plus 1 year, or as required by national
 legislation. Temperature mapping should show uniformity of the temperature across the
storage facility. It is recommended that temperature monitors be located in areas that are
most likely to show fluctuations.
4.19 Equipment used for monitoring should also be calibrated at defined intervals.

5. Storage requirements Documentation: written instructions and records

5.1 Written instructions and records should be available which document all activities in the
storage areas including the handling of expired stock. These should adequately describe the storage
procedures and define the route of materials and pharmaceutical products and information through the
organization in the event of a product recall being required.

5.2 Permanent information, written or electronic, should exist for each stored material or
product indicating recommended storage conditions, any precautions to be observed and retest dates.
Pharmacopoeial requirements and current national regulations concerning labels and containers should
be respected at all times.

5.3 Records should be kept for each delivery. They should include the description of the goods,
quality, quantity, supplier, supplier’s batch number, the date of receipt, assigned batch number and the
expiry date. Where national regulations prescribe that records must be retained for a certain period, this
must be observed. (Otherwise such records should be retained for a period equal to the shelf-life of the
incoming materials and products, where applicable, plus 1 year).

5.4 Comprehensive records should be maintained showing all receipts and issues of materials
and pharmaceutical products according to a specified system, e.g. by batch number.

Labelling and containers 5.5 All materials and pharmaceutical products should be stored in
containers which do not adversely affect the quality of the materials or products concerned, and which
offer adequate protection from external influences. In some circumstances, this could include bacterial
contamination.

5.6 All containers should be clearly labelled with at least the name of the material, the batch
number, the expiry date or retest date, the specified storage conditions and reference to the
pharmacopoeia, where applicable. Unauthorized abbreviations, names or codes should not be used.

Receipt of incoming materials and pharmaceutical products 5.7 On receipt, each incoming
delivery should be checked against the relevant purchase order and each container physically verified,
e.g. by the label description, batch number, type of material or pharmaceutical product and quantity.

5.8 The consignment should be examined for uniformity of the containers and, if necessary,
should be subdivided according to the supplier’s batch number should the delivery comprise more than
one batch.

5.9 Each container should be carefully inspected for possible contamination, tampering and
damage, and any suspect containers or, if necessary, the entire delivery should be quarantined for
further investigation.
 5.10 When required, samples should be taken only by appropriately trained and qualified
personnel and in strict accordance with written sampling instructions. Containers from which samples
have been taken should be labelled accordingly.

5.11 Following sampling, the goods should be subject to quarantine. Batch segregation should
be maintained during quarantine and all subsequent storage.

5.12 Materials and pharmaceutical products should remain in quarantine until an authorized
release or rejection is obtained.

5.13 Measures should be taken to ensure that rejected materials and pharmaceutical products
cannot be used. They should be stored separately from other materials and pharmaceutical products
while awaiting destruction or return to the supplier.

Stock rotation and control 5.14 Periodic stock reconciliation should be performed by comparing
the actual and recorded stocks.

5.15 All significant stock discrepancies should be investigated as a check against inadvertent
mix-ups and/or incorrect issue.

5.16 In manufacturing facilities, partly used containers of materials and pharmaceutical products
should be securely reclosed and resealed to prevent spoilage and/or contamination during subsequent
storage. Materials and pharmaceutical products from containers which have been opened or partly used
should be used up before those in unopened containers.

5.17 Damaged containers should not be issued unless the quality of the material has been
shown to be unaffected. Where possible, this should be brought to the attention of the person
responsible for quality control. Any action taken should be documented.

Control of obsolete and outdated materials and pharmaceutical products 5.18 All stocks should
be checked regularly for obsolete and outdated materials and pharmaceutical products. All due
precautions should be observed to prevent the issue of outdated materials and pharmaceutical
products.

6. Returned goods

6.1 Returned goods, including recalled goods, should be handled in accordance with approved
procedures and records should be maintained.

6.2 All returned goods should be placed in quarantine and returned to saleable stock only after this has
been approved by a nominated, responsible person following a satisfactory quality re-evaluation.

6.3 Any stock reissued should be so identified and recorded in stock records. Pharmaceuticals returned
from patients to the pharmacy should not be taken back as stock, but should be destroyed.

7. Dispatch and transport

7.1 Materials and pharmaceutical products should be transported in such a way that their integrity is not
impaired and that storage conditions are maintained.
7.2 Special care should be exercised when using dry ice in cold chains. In addition observing to safety
precautions, it must be ensured that the materials or product does not come in into contact with dry ice,
as this may adversely affect the product quality, e.g. by freezing.

7.3 Where appropriate, the use of devices to monitor conditions such as temperature during
transportation is recommended. Monitoring records should be available for review.

7.4 The dispatch and transport of materials and pharmaceutical products should be carried out only
after receipt of a delivery order. The receipt of the delivery order and the dispatch of the goods must be
documented.

7.5 Dispatch procedures should be established and documented, taking into account the nature of the
materials and pharmaceutical products concerned and any special precautions that might be required.

7.6 The outside container should offer adequate protection from all external influences and should be
indelibly and clearly labelled.

7.7 Records for dispatch should be retained, stating at least: 134 — the date of dispatch; — the
customer’s name and address; — the product description, e.g. name, dosage form and strength (if
appropriate), batch number and quantify; — the transport and storage conditions.

7.8 All records should be readily accessible and available on request.

8. Product recall 8.1 There should be a procedure to recall from the market, promptly and effectively,
pharmaceutical products and materials known or suspected to be defective.
GOOD STORAGE AND DISTRIBUTION PRACTICES FOR MEDICAL PRODUCTS, WHO

GOOD STORAGE AND DISTRIBUTION PRACTICES FOR MEDICAL PRODUCTS 1. INTRODUCTION

1.1 Storage and distribution are important activities in the supply chain management of medical
products. Various people and entities may be responsible for the handling, storage and distribution of
medical products. Medical products may be subjected to various risks at different stages in the supply
chain, for example, purchasing, storage, repackaging, relabelling, transportation and distribution.

1.2 Substandard and falsified products are a significant threat to public health and safety. Consequently,
it is essential to protect the supply chain against the penetration of such products.

1.3 This document sets out steps to assist in fulfilling the responsibilities involved in the different stages
within the supply chain and to avoid the introduction of substandard and falsified products into the
market. The relevant sections should be considered as particular roles that entities play in the storage
and distribution of medical products.

1.4 This guideline is intended to be applicable to all entitiesinvolvedin any aspect of the storage and
distribution of medical products, from the premises of the manufacturer of the medical product to his or
her agent, or the person dispensing or providing medical products directly to a patient. This includes all
entities involved in different stages of the supply chain of medical products, manufacturers and
wholesalers as well as brokers, suppliers, distributors, logistics providers, traders, transport companies
and forwarding agents and their employees.

1.5 The relevant sections of this guideline should also be considered for implementation by, amongst
others, governments, regulatory bodies, international procurement organizations, donor agencies and
certifying bodies, as well as all health care workers.

1.6 This guideline can be used as a tool in the prevention of the distributionof substandard and falsified
products. It should however be noted that these are general guidelines which may be adapted to suit
the prevailing situations and conditions in individual countries. National or regional guidelines may be
developed to meet specific needs and situations in a particular region or country. Consultation
Documents WHO Drug Information, Vol 33, No. 2, 2019

1.7 To maintain the quality of medical products, every party active in the supply chain has to comply
with the applicable legislation and regulations. Every activity in the storage and distribution of medical
products should be carried out according to the principles of good manufacturing practices (GMP) (1),
good storage practices (GSP) (2) and good distribution practices (GDP) (3), as applicable.

1.8 This guideline does not deal with dispensing to patients as this is addressed in the World Health
Organization (WHO) Good Pharmacy Practice (GPP) (4).

1.9 This guideline should also be read in conjunction with other WHO guidelines.

2. SCOPE

2.1 This document lays down guidelines for the storage and distribution of medical products. It is closely
linked to other existing guidelines recommended by the WHO Expert Committee on Specifications for
Pharmaceutical Preparations, such as referenced below.
2.2 Depending on the national and regional legislation, these guidelines may apply equally to medical
products for human and veterinary use.

2.3 The document does not specifically cover GMP aspects of finished products in bulk, distribution of
labels or packaging as these aspects are considered to be covered by other guidelines. The principles for
the distribution of starting materials (active pharmaceutical ingredients (APIs) and excipients) are also
not covered here. These are laid down in the WHO document Good Trade and Distribution Practices for
Pharmaceutical Starting Materials (5)

GLOSSARY The definitions provided below apply to the words and phrases used in this guideline.
Although an effort has been made to use standard definitions as far as possible, they may have different
meanings in other contexts and documents.

active pharmaceutical ingredient (API) -Any substance or mixture of substances intended to be used in
the manufacture of a pharmaceutical dosage form and that, when used in the production of a drug,
becomes an active ingredient of that drug. Such substances are intended to furnish pharmacological
activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to
affect the structure and function of the body.

ALCOA. A commonly used acronym for “attributable, legible, contemporaneous, original and accurate”.

auditing. An independent and objective activity designed to add value and improve an organization’s
operations by helping the organization to accomplish its objectives by using a systematic, disciplined
approach to evaluate and improve the effectiveness of risk management, control and governance
processes.

batch. A defined quantity of pharmaceutical products processed in a single process or series of

processes so that it is expected to be homogeneous.

batch number. A distinctive combination of numbers and/orletterswhichuniquelyidentifies a batch, for

example, on the labels, its batch records and corresponding certificates of analysis.

broker. Arranges transactions in relation to the sale or purchase of medical products that consist of
negotiating, independently and on behalf of another legal or natural person, and that do not include
physical handling.

consignment. The quantity of pharmaceutical products supplied at one time in response to a particular
request or order. A consignment may comprise of one or more packages or containers and may include
pharmaceutical products belonging to more than one batch.

container. The material employed in the packaging of a pharmaceutical product. Containers include
primary, secondary and transportation containers. Containers are referred to as primary if they are
intended to be in direct contact with the product. Secondary containers are not intended to be in direct
contact with the product.

contamination. The undesired introduction of impurities of a chemical or microbiological nature, or of

foreign matter, into or on to a starting material, intermediate or pharmaceutical product during
handling, production, sampling, packaging or repackaging, storage or transportation.
contract. Business agreement for the supply of goods or performance of work at a specified price.
Consultation Documents WHO Drug Information, Vol 33, No. 2, 2019 198 corrective and preventative
actions (CAPA). A system for implementing corrective and preventive actions resulting from an
investigation of complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory
inspections and findings and trends from process performance and product quality monitoring.

cross-contamination. Contamination of a starting material, intermediate product or finished

pharmaceutical product with another starting material or product during production, storage and
transportation.

distribution. The procuring, purchasing, holding, storing, selling, supplying, importing, exporting or
movement of pharmaceutical products, with the exception of the dispensing or providing
pharmaceutical products directly to a patient or his or her agent.

excipient. A substance, other than the active ingredient, which has been appropriately evaluated for
safety and is included in a drug delivery system to aid in the processing of the drug delivery system
during its manufacture; protect, support or enhance stability, bioavailability, or patient acceptability;
assist in product identification; or enhance any other attribute of the overall safety and effectiveness of
the drug during storage or use.

expiry date. The date given on the individual container (usually on the label) of a pharmaceutical
product up to and including the date on which the product is expected to remain within specifications, if
stored correctly. It is established for each batch by adding the shelf life to the date of manufacture.

falsified product. A product that has been deliberately and/or fraudulently misrepresented as to its
identity, composition or source. Such deliberate/fraudulent misrepresentation refers to any
substitution, adulteration, reproduction of an authorized product or the manufacture of a product that
is not an authorized product.

first expiry/first out (FEFO). A distribution procedure that ensures that the stock with the earliest expiry
date is distributed and/or used before an identical stock item with a later expiry date is distributed
and/or used.

forwarding agent. A person or entity engaged in providing, either directly or indirectly, any service
concerned with clearing and forwarding operations in any manner to any other person and includes a
consignment agent.

good distribution practices (GDP). Thatpart ofquality assurance that ensuresthatthequality of a

pharmaceutical product is maintained by means of adequate control of the numerous activities which
occur during the distribution process, as well as providing a tool to secure the distribution system from
falsified, unapproved, illegally imported, stolen, substandard, adulterated and/or misbranded
pharmaceutical products.

good manufacturing practices (GMP). That part of quality assurance which ensures that pharmaceutical
products are consistently produced and controlled to the quality standards appropriate to their
intended use and as required by the marketing authorization.
good pharmacy practice (GPP). The practice of pharmacy aimed at providing and promoting the best use
of medicines and other health care services and products by patients and members of the public. It
requires that the welfare of the patient is the pharmacist’s prime concern at all times.

good practices (GXP). Acronym for the group of good practice guides governing the preclinical, clinical,
manufacturing, testing, storage, distribution and post-market activities for regulated pharmaceuticals,
biologicals and medical devices, such as good laboratory practices (GLP), good clinical practices (GCP),
good manufacturing practices (GMP), good pharmacovigilance practices (GPP) and good distribution
practices (GDP).

good storage practices (GSP). That part of quality assurance that ensuresthat the quality of
pharmaceutical products is maintained by means of adequate control throughout the storage thereof.

good trade and distribution practices (GTDP). That part of quality assurance that ensuresthat the quality
of pharmaceutical productsis maintainedbymeansofadequate control throughoutthenumerous activities
which occur during the trade and the distributionprocess.

heating, ventilation and air conditioning systems (HVAC). Heating, ventilation and air-conditioning, also
referred to as environmental control system (ECS).

importation. The act of bringing or causing any goods to be brought into a customs territory (national
territory, excluding any free zone).

intermediate product. Partly processed product that must undergo further manufacturing steps before
it becomes a bulk finished product.

labelling. Process of identifying a pharmaceutical product including the following information, as

appropriate: name of the product; active ingredient(s), type and amount; batch number; expiry date;
special storage conditions or handling precautions; directions for use, warnings and precautions; names
and addresses of the manufacturer and/or the supplier.

manufacture. All operations of purchase of materials and products, production, packaging, labelling,
quality control,release,storage and distribution of pharmaceutical products and the related controls.

marketing authorization. A legal document issued by the national regulatory authority forthe purpose of
marketing or free distribution of a product after evaluation for safety, efficacy and quality. It must set
out, inter alia, the name of the product,thepharmaceuticaldosage form,thequantitative formula
(including excipients) per unit dose (using International Nonproprietary Names(INNs) or national generic
names where they exist), the shelf life and storage conditions, and packaging characteristics, or other
details as required by the product category. It specifies the information on which authorization is based
(e.g. “The product(s) must conform to all the details provided in your application and as modified in
subsequent correspondence”). It also contains the product information approved for health
professionals and the public, the sales category, the name and address of the holder of the authorization
and the period of validity of the authorization. Once a product has beengivenmarketing authorization,
itisincluded on a list of authorized products - the register- and is often said to be “registered” or to “have
registration”. Market authorization may occasionally also be referred to as a “licence” or “product
licence”.
material. A general term used to denote starting materials (APIs and excipients), reagents, solvents,
process aids, intermediates, packaging materials and labelling materials.

medical products. Products including, but not limited to, finished pharmaceutical products, medical
devices, vaccines and in vitro diagnostics (IVDs).

packaging material. Any material, including printed material, employed in the packaging of a
pharmaceutical product, but excluding any outer packaging used for transportation or shipment.
Packaging materials are referred to as primary or secondary according to whether or not they are
intended to be in direct contact with the product.

pedigree. A complete record that tracesthe ownership of and transactionsrelating to a pharmaceutical

product as it is distributed through the supply chain.

pharmaceutical product. Any product intended for human use, or veterinary product intended for
administration to food-producing animals, presented in its finished dosage form, which is subject to
control by pharmaceutical legislation in either the exporting or the importing state and includes
products for which a prescription is required, products which may be sold to patients without a
prescription, biologicals and vaccines. It does not, however, include medical devices.

product recall. A process for withdrawing or removing a pharmaceutical product from the
pharmaceutical distribution chain because of defects in the product, complaints of serious adverse
reactions to the product and/or concerns that the product is or may be falsified. The recall might be
initiated by the manufacturer, importer, wholesaler, distributor or a responsible agency.

production. All operations involved in the preparation of a pharmaceutical product, from receipt of
materials through processing, packaging and repackaging, labelling and relabelling, to completion of the
finished product.

quality assurance. A wide-ranging concept covering all mattersthatindividually or collectively influence

the quality of a product. It isthe totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use.

quality risk management. A systematic process for the assessment, control, communication and review
of risks to the quality of pharmaceutical products across the product life cycle.

quality system. An appropriate infrastructure, encompassing the organizational structure, procedures,

processes and resources and systematic actions necessary to ensure adequate confidence that a product
(or services) will satisfy given requirements for quality.

quarantine. The status of pharmaceutical products isolated physically or by other effective means while
a decision is awaited on their release, rejection or reprocessing.

retest date. The date when a material should be re-examined to ensure that it is still suitable for use.

sampling. Operations designed to obtain a representative portion of a pharmaceutical product, based on

an appropriate statistical procedure, for a defined purpose, for example, acceptance of consignments or
batch release.
self-inspection. Self-inspection is an internal procedure followed to evaluate the entity's compliance
with GSDP and GXP in all areas of activities, designed to detect any shortcomings and to recommend
and implement necessary corrective actions.

shelf life. The period of time during which a pharmaceutical product, if stored correctly, is expected to
comply with the specification as determined by stability studies on a number of batches of the product.
The shelf life is used to establish the expiry date of each batch.

standard operating procedure (SOP). An authorized written procedure giving instructions for performing
operations not necessarily specific to a given product but of a moregeneral nature (e.g. equipment
operation, maintenance and cleaning, validation, cleaning of premises and environmental control,
sampling and inspection).

storage. The storing of pharmaceutical products up to the point of use.

substandard products. “Substandard” medical products (also called “out of specification”) are
authorized by national regulatory authorities but fail to meet either national or international quality
standards or specifications – or, in some cases, both.

supplier. A person or entity engaged in the activity of providing products and/or services.

transit. The period during which pharmaceutical products are in the process of being carried, conveyed,
or transported across, over or through a passageor route to reach the destination.

vehicles. Trucks, vans, buses, minibuses, cars, trailers, aircraft, railway carriages, boats and other means
which are used to convey pharmaceutical products

4. GENERAL PRINCIPLES

4.1 There should be collaboration between all entities, including governments, customs agencies, law
enforcement agencies, regulatory authorities, manufacturers, distributors and entities responsible for
the supply of medical products to patients to ensure the quality and safety of medical products; to
prevent the exposure of patients to substandard and falsified products and to ensure that the integrity
of the distribution chain is maintained.

4.2 The principles of GSP and GDP should be included in national legislation and guidelines for the
storage and distribution of medical products in a country or region, as applicable, as a means of
establishing minimum standards. The principles of GSP and GDP are applicable to: • medical products
moving forward in the distribution chain from the manufacturer; • medical products which are moving
backwards in the chain, for example, as a result of the return or recall thereof; and • donations of
medical products.

5. QUALITY MANAGEMENT Quality Systems

5.1 Entities involved in the storage and distribution of medical products should have a comprehensively
designed, documented and correctly implemented quality system that incorporates good storage
practices, good distribution practices, quality risk management principles and management review.

5.2 Senior management has the ultimate responsibility to ensure that an effective quality system is
established, resourced, implemented and maintained.
5.3 The quality system should ensure that: • GSP and GDP are adopted and implemented to ensure that
the quality of medical products is maintained throughout their shelf-life in the supply chain; medical
products are appropriately procured, stored, distributed and delivered (in compliance with the
legislation) to the appropriate recipients; (see 18.1) • operations are clearly specified in written
procedures; • responsibilities are clearly specified in job descriptions; • all risks are identified, and
necessary, effective controls are implemented; • processes are in place to assure the management of
outsourced activities; • there is a procedure for self-inspection and quality audits; • there is a system for
quality risk management (QRM); • there are systems for managing returns, complaints and recalls; •
there are systems to manage changes, deviations and corrective and preventive actions (CAPAs).

5.4 There should be an authorized, written quality policy describing the overall intentions and
requirements regarding quality. This may be reflected in a quality manual.

5.5 There should be an appropriate organizational structure. This should be presented in an authorized
organizational chart. The responsibility, authority and interrelationships of personnel should be clearly
indicated.

5.6 Roles and responsibilities should be clearly defined and understood by the individuals concerned
and recorded as written job descriptions.

5.7 The quality system should include appropriate procedures, processes and resources.

7. MANAGEMENT REVIEW

7.1 There should be a system for periodic management review. The review should include at least: •
senior management; • review of the quality system and its effectiveness by using quality metrics and key
performance indicators; • identification of opportunities for continual improvement; and • follow-up on
recommendations from previous management review meetings.

7.2 Minutes and related documentation from management review meetings should be available.

8. COMPLAINTS

8.1 There should be a written procedure for the handling of complaints. In the case of a complaint about
the quality of a medical product or its packaging, the original manufacturer and/or marketing
authorization holdershould be informed as soon as possible.

8.2 All complaints should be recorded and appropriately investigated. The root cause should be
identified and the impact (e.g. on other batches or products) risk assessed. Appropriate CAPAs should be
taken.

8.3 Where required, the information should be shared with the national regulatory authority and a recall
initiated where appropriate.

8.4 A distinction should be made between complaints about a medical product or its packaging and
those relating to distribution.

8.5 The relevant information, such as the results of the investigation of the complaint, should be shared
with the relevant entities.
8.6 Medical product quality problems and suspected cases of substandard or falsified products identified
should be handled according to relevant authorized procedures. The information should be shared with
the manufacturer and appropriate national and/or regional regulatory authorities without delay

9. RETURNED GOODS

9.1 Returned medical products should be handled in accordance with authorized procedures.

9.2 All returned medical products should be placed in quarantine upon receiving. The status of the
goods should be clear. Precautions should be taken to prevent access and distribution until a decision
has been taken with regard to their disposition. The particular storage conditions applicable to the
medical products should be maintained.

9.3 Medical products returned should be destroyed unless it is certain that their quality is satisfactory
after they have been critically assessed in accordance with a written and authorized procedure.

9.4 The nature of the medical product, any special storage conditions it requires, its condition and
history and the time lapse since it was issued, should all be taken into account in this assessment. Where
any doubt arises over the quality of the medical product, it should not be considered suitable for reissue
or reuse. Any action taken should be appropriately recorded.

9.5 When handling returned goods, the following considerations at least should be taken: • A risk-based
process should be followed when deciding on the fate of the returned goods. This should include, but
not be limited to, the nature of the product, storage conditions, condition of the product history, time-
lapse since distribution and the manner and condition of transport while being returned. • The terms
and conditions of the agreement between the parties. • Examination of the returned goods, with
decisions taken by suitably qualified, experienced and authorized persons.

9.6 Where products are rejected, authorized procedures should be followed, including safe transport.

9.7 Destruction of products should be done in accordance with international, national and local
requirements regarding disposal of such products and with due consideration to the protection of the
environment.

9.8 Records of all returned, rejected and destroyed medical products should be kept for a defined period
in accordance with national requirements.

10. RECALLS

10.1 There should be a written procedure, in compliance with national or regional requirements, to
effectively and promptly recall medical products.

10.2 The effectiveness of the procedure should be checked annually and updated as necessary.

10.3 Theoriginalmanufacturerand/ormarketingauthorizationholder, or other relevant contract party,

should be informed in the event of a recall.

10.4 Information on a recall should be shared with the appropriate national or regional regulatory
authority.
10.5 All recalled products should be secure, segregated, transported and stored under appropriate
conditions. These should be clearly labelled asrecalled products. The particular storage conditions
applicable to the product should be maintained.

10.6 All customers and competent authorities of all countries to which a given medical product may
have been distributed should be informed promptly of the recall of the product.

10.7 All records, including distribution records, should be readily accessible to the designated person(s)
responsible for recalls. These records should contain sufficient information on products supplied to
customers (e.g. name, address, contact detail, batch numbers, quantities and safety features - including
exported products).

10.8 The progress of a recall process should be recorded and a final report issued which includes a
reconciliation between delivered and recovered quantities of medical products.

11. SELF-INSPECTION

11.1 The quality system should include self-inspections. These should be conducted to monitor the
implementation, compliance with and effectiveness of SOPs as well as compliance with regulations, GSP,
GDP and other appropriate guidelines.

11.2 Self-inspections should be conducted periodically according to an annual schedule.

11.3 The team conducting the inspection should be free from bias and individual members should have
appropriate knowledge and experience

11.4 The results of allself-inspectionsshould be recorded. Reportsshould contain all observations made
during the inspection and presented to the relevant personnel and management.

11.5 Necessary CAPAs should be taken and the effectiveness of the CAPAs should be reviewed.

12. PREMISES General

12.1 Premises should be suitably located, designed, constructed and maintained to ensure appropriate
operations such as receiving, storage, picking, packing and dispatch of medical products.

12.2 There should be sufficient space, lighting and ventilation to ensure required segregation,
appropriate storage conditions and cleanliness.

12.3 Sufficient security should be provided, and access should be controlled.

12.4 Appropriate controls and segregation should be provided for products requiring specific handling or
storage conditions such as radioactive materials, products containing hazardous substances and
products to be stored under controlled temperature and relative humidity conditions.

12.5 Receiving and dispatch bays should be separate and should protect products from weather
conditions.

12.6 Activities relating to receiving and dispatch should be done in accordance with authorized
procedures. Areas should be suitably equipped for the operations.
12.7 Premises should be kept clean. Cleaning equipment and cleaning agents should not become
possible sources of contamination.

12.8 Premises should be protected from the entry of birds, rodents, insects and other animals. A rodent
and pest control programme should be in place.

12.9 Toilets, wash, rest and canteen facilities should be separate from other areas. Food, eating,
drinking and smoking should be prohibited in all areas where medical products are stored or handled.

Receiving

12.10 Each incoming delivery should be checked against the relevant documentation to ensure that the
correct product is delivered from the correct supplier. This may include, for example, the purchase
order, containers, label description, batch number, expiry date, product and quantity.

12.11 The consignment should be examined for uniformity of the containers and, if necessary, should be
subdivided according to the supplier’s batch number should the delivery comprise more than one batch.
Each batch should be dealt with separately.

12.12 Each container should be carefully checked for possible contamination, tampering and damage.
Any suspect containers or, if necessary, the entire delivery should be quarantined for further
investigation.

12.13 Receiving areas should be of sufficient size to allow the cleaning of incoming medical products.

12.14 When required, samples of medical products should be taken by appropriately trained and
qualified personnel and in strict accordance with a written sampling procedure and sampling plans.
Containers from which samples have been taken should be labelled accordingly.

12.15 Following sampling, the goods should be subject to quarantine. Batch segregation should be
maintained during quarantine and all subsequent storage.

12.16 Materials and products requiring storage under controlled conditions of temperature and relative
humidity, as applicable, should be handled as a priority. 12.17 Medical products should not be
transferred to saleable stock until an authorized release is obtained.

12.18 Measures should be taken to ensure that rejected medical products cannot be used. They should
be segregated and securely stored while awaiting destruction or return to the supplier.

Storage areas

12.19 Precautions should be taken to prevent unauthorized persons from entering storage areas.

12.20 Storage areas should be of sufficient capacity to allow the orderly storage of the various
categories of medical products. 1

2.21 Storage areas should be appropriately designed, constructed, maintained or adapted. They should
be kept clean and there should be sufficient space and lighting.
12.22 Storage areas should be maintained within acceptable and specified temperature limits. Where
special storage conditions are required on the label (e.g. temperature, relative humidity), these should
be provided, controlled, monitored and recorded.

12.23 Medical products should be stored off the floor and suitably spaced to permit ventilation, cleaning
and inspection. Suitable pallets should be used and kept in a good state of cleanliness and repair.

12.24 A written sanitation programme should be available indicating the frequency of cleaning and the
methods to be used to clean the premises and storage areas.

12.25 There should be appropriate procedures for the clean-up of any spillage to ensure complete
removal of any risk of contamination.

12.26 Where the status is ensured by storage in separate areas, these areas should be clearly marked,
and their access restricted to authorized personnel. Any system replacing physical separation and
labelling, or demarcation should provide equivalent security. For example, computerized systems can be
used provided that they are validated to demonstrate security of access (6).

12.27 Sampling should be done under controlled conditions and conducted in such a way that there is
no risk of contamination or cross-contamination. Adequate cleaning procedures should be followed
after sampling.

12.28 Certain materials and products such as highly active and radioactive materials, narcotics and other
hazardous, sensitive and/or dangerous materials and products, as well as substances presenting special
risks of abuse, fire or explosion (e.g. combustible liquids and solids and pressurized gases), should be
stored in a dedicated area that is subject to appropriate additional safety and security measures; and in
accordance with national legislation

12.29 Medical products should be handled and stored in such a manner as to prevent contamination,
mix-ups and cross-contamination.

12.30 Medical products should be stored in conditions which assure that their quality is maintained.
Stock should be appropriately rotated. The “first expired/first out” (FEFO) principle should be followed.

12.31 Narcotic medical products should be stored in compliance with international conventions,
national laws and regulations on narcotics.

12.32 Broken or damaged items should be withdrawn from usable stock and separated. 12.33 There
should be appropriate procedures for the clean-up of any spillage to ensure complete removal of any
risk of contamination. Storage conditions

12.34 The storage conditions for medical products should be in compliance with their labelling.

12.35 Heating, ventilation and air conditioning systems (HVAC) should be appropriately designed,
installed, qualified and maintained to ensure that the required storage conditions are maintained (7).

12.36 Mapping studies for temperature and relative humidity, as appropriate, should be done (8). This
applies, for example, to areas, refrigerators and freezers.

12.37 Temperature and relative humidity, as appropriate, should be controlled and monitored at regular
intervals. Data should be recorded, and the records should be reviewed. The equipment used for
monitoring should be calibrated and be suitable for their intended use. All records pertaining to
mapping and monitoring should be kept for a suitable period of time and as required by national
legislation.

13. STOCK CONTROL AND ROTATION

13.1 Periodic stock reconciliation should be performed at defined intervals by comparing the actual and
recorded stock.

13.2 The root cause for stock discrepancies should be identified and appropriate CAPAs taken to prevent
recurrence.

13.3 When damaged containers are received, this should be brought to the attention of the person
responsible for quality. Any action taken should be documented. (These containers should not be issued
unless the quality of the medical products has been shown to be unaffected).

13.4 All stock should be checked regularly to identify obsolete, to be retested, and expired stock.

14. EQUIPMENT

14.1 Equipment, including computerized systems should be suitable for their intended use. These should
be appropriately designed, located, installed, qualified and maintained.

14.2 Computerized systems should be capable of achieving the desired output and results.

14.3 Where electronic commerce (e-commerce) is used, i.e. electronic means for any of the steps,
defined procedures and adequate systems should be in place to ensure traceability and confidence in
the supply chain and products concerned.

14.4 Electronic transactions (including those conducted via the Internet) relating to the distribution of
medical products should be performed only by authorized persons according to defined and authorized
access and privileges.

14.5 Where GXP systems are used, these should meet the requirements of WHO and other guidelines on
computerized systems (6,9).

15. QUALIFICATION AND VALIDATION

15.1 The scope and extent of qualification and validation should be determined using documented risk
management principles.

15.2 Premises, utilities, equipment and instruments, processes and procedures should be considered.
The scope and extent of qualification and validation in case of any significant changes should be
identified.

15.3 Qualification and validation should be done following procedures and protocols. The results and
outcome of the qualification and validation should be recorded in reports. Deviations should be
investigated, and the completion of the qualification and validation should be concluded and approved.

16. PERSONNEL

16.1 There should be an adequate number of personnel.

16.2 Personnel should have appropriate educational qualification, experience and training relative to the
activities undertaken.

16.3 Personnel should have the authority and resources needed to carry out their duties and to follow
the quality systems, as well as to identify and correct deviations from the established procedures.

16.4 There should be arrangements in place to ensure that management and personnel are not
subjected to commercial, political, financial and other pressures or conflict of interest that may have an
adverse effect on the quality of service provided or on the integrity of medical products.

16.5 Safety procedures should be in place relating to all relevant personnel and property,
environmental protection and product integrity.

16.6 Personnel should receive initial and continued training in accordance with a written training
programme. The training should cover the requirements of GSP, GDP ( as applicable), as well as on-the-
job training. Other topics should be included, such as product security, product identification and the
detection of falsified products.

16.7 Personnel dealing with hazardous products (such as highlyactivematerials,radioactive

materials,narcotics andotherhazardous, environmentally sensitive and/or dangerous pharmaceutical
products, as well as products presenting special risks of abuse, fire or explosion) should be given specific
training.

16.8 Personnel should be trained in, and observe high levels of, personal hygiene and sanitation.

16.9 Records of alltraining, attendance and assessments should be kept.

16.10 Personnel handling products shouldwear garmentssuitable for the activitiesthat they perform.
Personnel dealing with hazardous pharmaceutical products, including products containing materials that
are highly active, toxic, infectious or sensitizing, should be provided with protective garments as
necessary.

16.11 Appropriate procedures relating to personnel hygiene, relevant to the activities to be carried out,
should be established and observed. Such procedures should cover health, hygiene and the clothing of
personnel.

16.12 Procedures and conditions of employment for employees, including contract and temporary staff,
and other personnel having access to medical products, must be designed and implemented to assist in
minimizing the possibility of such products coming into the possession of unauthorized persons or
entities.

16.13 Codes of practice and punitive procedures should be in place to prevent and address situations
where persons involved in the storage and distribution of medical products are suspected of, or found to
be implicated in, any activities relating to the misappropriation, tampering, diversion or falsifying of any
product.

17. DOCUMENTATION
 17.1 Documentation includes all procedures, records and data, whether in paper or electronic form.
Documents should be appropriately designed, completed, reviewed, authorized, distributed and kept as
required. Documents should be readily available.

17.2 Written procedures should be followed for the preparation, review, approval, use of and control of
all documents relating to the policies and activities for storage and distribution of medical products
process.

17.3 Documents should be laid out in an orderly fashion and be easy to complete, review and check. The
title, scope, objective and purpose of each document should be clear.

17.4 The contents of documents should be accurate, legible, traceable, attributable and unambiguous.

17.5 All documents should be completed, signed and dated as required by authorized person(s) and
should not be changed without the necessary authorization.

17.6 Documentation should be prepared and maintained in accordance with the national legislation and
principles of good documentation practices (9).

17.7 Data should meet ALCOA principles. Procedures should be followed, and records maintained for
the back-up and restoration of data.

17.8 The distributor must establish and maintain procedures for the identification, collection,
indexing,retrieval,storage, maintenance, disposal of and access to all applicable documentation.

17.9 Documentsshould be reviewed regularly and kept up-to-date. When a document has been revised,
a system should exist to prevent inadvertent use of the superseded version.

17.10 All records should be stored and retained using facilities that prevent unauthorized access,
modification, damage, deterioration and/or loss of documentation during the entire life cycle of the
record. Records must be readily retrievable.

17.11 Comprehensive records should be maintained for all receipts, storage, issues and distribution. The
records should include, for example: • date (e.g. receipt or dispatch, as appropriate); • name and
description of the product; • quantity received, or supplied; • name and address of the supplier and
customer. • batch number(s); • expiry date; • suitability of the supplier; • qualification of suppliers; and
• customer qualification

17.12 All containers should be clearly labelled with at least the name of the medical product, batch
number, expiry date or retest date, and the specified storage conditions.

18. ACTIVITIES AND OPERATIONS

18.1 All activities and operations should be conducted in accordance with national legislation, GSP, GDP
and associated guidelines.

18.2 Storage and distribution of medical products should be done by persons so authorized, in
accordance with national legislation.

18.3 Activities and operations should be performed in accordance with documented procedures.
18.4 Automated Storage and Retrieval Systems (AS/RS) and operations should comply with current GSP,
GDP and GXP guidelines, as well as the recommendations in this guideline.

Receiving

18.5 Medical products should be procured from appropriately authorized suppliers.

18.6 Deliveries should be examined for damage, seal intactness, signs of tampering, labelling,
completeness of order and other related aspects, at the time of receiving.

18.7 Containers and consignments not meeting acceptance criteria at the time of receipt should be
labelled, kept separate and investigated. This includes suspected falsified products.

Storage

18.8 Medical products requiring specific storage conditions, or controlled access, (e.g. narcotics) should
be processed without delay and stored in accordance with their requirements.

18.9 Appropriate controls should be implemented to prevent contamination and/or mix ups during
storage.

18.10 Controls and procedures should be in place to prevent and handle spillage and breakage.

Repackaging and relabelling

18.11 Repackaging and relabelling of materials and products are not recommended. Where repackaging
and relabelling occur, these activities should only be performed by entities appropriately authorized to
do so and in compliance with the applicable national, regional and international requirements, and in
accordance with GMP.

18.12 Procedures should be in place for the controlled disposal of original packaging to prevent re-use
thereof.

Distribution and transport

18.13 Medical products should be transported in accordance with the conditions stated on the labels.
There should be no risk to the quality of the medical product during transport and distribution.

18.14 Product, batch and container identity should be maintained at all times.

18.15 All labels should remain legible.

18.16 Distribution records should be sufficiently detailed to allow for a recall when required.

18.17 Drivers of vehicles should be identified and present appropriate documentation to demonstrate
that they are authorized to transport medical products.

18.18 Vehicles should be suitable for their purpose, with sufficient space and appropriately equipped to
protect medical products.

18.19 The design and use of vehicles and equipment must aim to minimize the risk of errors and permit
effective cleaning and/or maintenance to avoid contamination, build-up of dust or dirt and/or any
adverse effect on the quality of the products.
18.20 Where feasible, consideration should be given to adding technology, such as global positioning
system (GPS) electronic tracking devices and engine-kill buttons to vehicles, which would enhance the
security and traceability of vehicles with products.

18.21 Where possible, dedicated vehicles and equipment should be used for medical products. Where
non-dedicated vehicles and equipment are used, procedures should be in place to ensure that the
quality of the products will not be compromised. Defective vehicles and equipment should not be used.
These should either be labelled as such or removed from service.

18.22 There should be procedures in place for the operation and maintenance of all vehicles and
equipment.

18.23 Equipment and materials used for the cleaning of vehicles should not become a source of
contamination or have an adverse effect on product quality.

18.24 Appropriate environmental conditions should be maintained, monitored and recorded. All
monitoring records should be kept for a defined period of time as required by national legislation.
Records of monitoring data should be made available for inspection by the regulatory or other oversight
body.

18.25 Instruments used for monitoring conditions, for example, temperature and humidity, within
vehicles and containers should be calibrated at regular intervals.

18.26 Rejected, recalled and returned products, as well as those suspected as being falsified, should be
securely packaged, clearly labelled and be accompanied by the appropriate supporting documentation.

18.27 Measures should be in place to prevent unauthorized persons from entering and/or tampering
with vehicles and/or equipment, as well as to prevent the theft or misappropriation thereof.

18.28 Shipment containers should have no adverse effect on the quality of the medical products and
should offer adequate protection to materials and these products. Containers should be labelled
indicating, for example, handling and storage conditions, precautions, contents and source, and safety
symbols, as appropriate.

18.29 Special care should be taken when using dry ice and liquid nitrogen in shipment containers due to
safety issues and possible adverse effects on the quality of medical products.

18.30 Written procedures should be available for the handling of damaged and/or broken shipment
containers. Particular attention should be paid to those containing potentially toxic and hazardous
products.

Dispatch

18.31 There should be documented, detailed procedures for the dispatch of products.

18.32 Medical products should only be sold and/or distributed to persons or entities that are authorized
to acquire such products in accordance with the applicable national legislation. Written proof of such
authorization must be obtained prior to the distribution of products to such persons or entities.

18.33 Dispatch and transportation should be undertaken only after the receipt of a valid order which
should be documented.
18.34 Records for the dispatch of products should be prepared and should include information such as,
but not limited to: • date of dispatch; • complete business name and address (no acronyms), type of
entity responsible for the transportation, telephone number, names of contact persons; • status of the
addressee (e.g. retail pharmacy, hospital or community clinic); • a description of the products including,
for example, name, dosage form and strength (if applicable); • quantity of the products, i.e. number of
containers and quantity per container (if applicable); • applicable transport and storage conditions; • a
unique number to allow identification of the delivery order; and • assigned batch number and expiry
date (where not possible at dispatch, this information should at least be kept at receipt to facilitate
traceability).

18.35 Records of dispatch should contain sufficient information to enable traceability of the product.
Such records should facilitate the recall of a batch of a product, if necessary, as well as the investigation
of falsified or potentially falsified products. In addition, the assigned batch number and expiry date of
products should be recorded at the point of receipt to facilitate traceability.

18.36 Vehicles and containers should be loaded carefully and systematically on a last-in/firstout (LIFO)
to save time when unloading, to prevent physical damage and to reduce security risks. Extra care should
be taken during loading and unloading of cartons to avoid damage.

18.37 Medical products should not be supplied or received after their expiry date, or so close to the
expiry date that this date is likely to be reached before the products are used by the consumer (10).

18.38 Medical products and shipment containers should be secured in order to prevent or to provide
evidence of unauthorized access. Vehicles and operators should be provided with additional security
where necessary, to prevent theft and other misappropriation of products during transportation.

18.39 Medical Products should be stored and transported in accordance with procedures such that: •
the identity of the product is not lost; • the product does not contaminate and is not contaminated by
other products; • adequate precautions are taken against spillage, breakage, misappropriation and
theft; and • appropriate environmental conditions are maintained, for example, using cold chain for
thermolabile products.

18.40 Written procedures should be in place for investigating and dealing with any failure to comply
with storage requirements, for example, temperature deviations. If a deviation has been noticed during
transportation by the person or entity responsible for transportation, this should be reported to the
distributor and recipient. In cases where the recipient notices the deviation, it should be reported to the
distributor.

18.41 Transportation of products containing hazardous substances or narcotics and other dependence-
producing substances, should be transported in safe, suitably designed, secured containers and vehicles.
In addition, the requirements of applicable international agreements and national legislation should be
met.

18.42 Spillages should be cleaned up as soon as possible in order to prevent possible contamination,
cross-contamination and hazards. Written procedures should be in place for the handling of such
occurrences.
18.43 Damage to containers and any other event or problem that occurs during transit must be
recorded and reported to the relevant department, entity or authority and investigated.

18.44 Products in transit must be accompanied by the appropriate documentation.

19. OUTSOURCED ACTIVITIES

19.1 Any activity relating to the storage and distribution of a medical product which is delegated to
another person or entity should be performed by the parties appropriately authorized in accordance
with national legislation and the terms of a written contract.

19.2 There should be a written contract between the entities. The contractshould define the
responsibilities of each entity (contract giver and contract acceptor) and cover at least the following: •
compliance with this guideline and the principles of GSP and GDP; • responsibilities of all entities for
measures to avoid the entry of substandard and falsified products into the distribution chain; • training
of personnel; • conditions of subcontracting subject to the written approval of the contract giver; and •
periodic audits.

19.3 The contract giver should assess the competence of the contract acceptor before entering into the
contract.

19.4 The contract giver should provide all relevant information relating to the material/ products to the
contract acceptor.

19.5 The contract acceptor should have adequate resources (e.g. premises, equipment, personnel,
knowledge, experience and vehicles, as appropriate) to carry out the work.

19.6 The contract acceptor should refrain from performing any activity that may adversely affect the
materials or products handled.

20. SUBSTANDARD AND FALSIFIED PRODUCTS

20.1 The quality system should include procedures to assist in identifying and handling medical products
that are suspected to be substandard and/or falsified.

20.2 Where such medical products are identified, the holder of the marketing authorization, the
manufacturer and the appropriate national, regional and international regulatory bodies (as
appropriate), as well as other relevant competent authorities,should be informed.

20.3 Such products should be stored in a secure, segregated area and clearly identified to prevent
further distribution or sale. Access should be controlled.

20.4 Records should be maintained reflecting the investigations and action taken, such as disposal of the
product. Falsified products should not re-enterthe market.

21. INSPECTION OF STORAGE AND DISTRIBUTION FACILITIES

21.1 Storage and distribution facilities should be inspected by inspectors so authorized by national
legislation. This should be done at determined, periodic intervals.

21.2 Inspectors should have appropriate educational qualifications, knowledge and experience (11).
21.3 An inspection should normally be conducted by a team of inspectors.

21.4 Inspectors should assess compliance with national legislation, GSP, GDP and related guidelines
(GXP) as appropriate.

21.5 Inspections should cover the premises, equipment, personnel, activities, quality system,
qualification and validation and other related aspects as contained in this guideline.

21.6 An inspection report should be prepared and provided to the inspected entity within a defined
period of time from the last day of the inspection. Observations may be categorized based on risk
assessment.

21.7 CAPA for observations listed as non-compliances in the inspection report, with the national
legislation and guidelines, should be submitted for review by the inspectors within the defined period as
stated by the inspectors.

21.8 Inspections should be closed with a conclusion after the review of the CAPAs.
HOSPITAL PHARMACY MANAGEMENT MANUAL OF DOH CHAPTER 8