Product Trend Requirements

Organizations, no matter what industry they’re in, generate a

significant amount of data as a result of running their business. This

situation is certainly true of the pharmaceutical industry. Good

manufacturing practices (GMP) regulations worldwide require

pharmaceutical companies to generate a significant body of data

related to all their activities, from the receipt of starting materials

through the distribution (and return) of finished products. A large

amount of data is generated around the quality of the finished

product, both at release for distribution and throughout the

established shelf life of the product.

Regulatory agencies around the world recognize that there is value in

the data that are generated or obtained (for example, through receipt

of returned goods or product complaints) as a result of complying with

GMP regulations. It is this acknowledgment, as well as the

recognition that it is important to critically assess the “health” of each

pharmaceutical product, that resulted in the regulatory requirement

for some form of annual assessment. The goals of the annual

assessments are to:

• Confirm that the products and associated processes remain in

a state of control

• Identify the need for changes to the products or processes

• Recognize opportunities for continuous improvement

Companies that undertake these reviews simply to meet their

regulatory obligations may miss out on the opportunities for

continuous improvement.

REGULATIONS

The United States Food and Drug Administration (FDA) requirement

to conduct an annual product review (APR) is found in 21 CFR

211.180(e). As the name suggests, FDA GMP regulations require

that pharmaceutical companies, on an annual basis (or, minimally,

one time per year), complete a thorough review of data associated

with each pharmaceutical product.

The European requirement to conduct a product quality review (PQR)

is found in Chapter 1 of Volume 4, European Union Guidelines to

GMP (as well as Chapter 1 of the PIC/S [Pharmaceutical Inspection

Convention and the Pharmaceutical Inspection Co-operation

Scheme] PE-009-11 PIC/S GMP Guide—Part I, Guide for Medicinal

Products). Similarly to the FDA requirement, pharmaceutical

companies must, on an annual basis, complete a thorough review of

specified data elements. Unlike the FDA GMP requirements,

however, this annual assessment must take into account data from

previous review periods (previous years). The data elements that

must be reviewed differ from the FDA requirements.

ANNUAL PRODUCT REVIEWS

General Requirements

FDA GMP regulations specify that pharmaceutical companies

maintain records associated with the production, control, or

distribution of each batch of drug product and retain those records for

at least one year after the expiration date of the batch (or, in the case

of certain over-the-counter [OTC] drug products, three years after

distribution of the batch). Additional records related to raw materials,

packaging containers, closures, and labeling must be retained

according to a similar timeline. The data associated with these

records are used for evaluating, at least annually, the quality

standards of each drug product.

Under FDA requirements, pharmaceutical companies are required to

establish a written procedure for conducting annual evaluations and

for ensuring that their procedure is followed as written. Additionally,

while not specifically identified in the regulations, firms should

document the results of each APR in a written report and submit the

reports to senior management for review. The reports typically

include summary conclusions on the quality of the product and any

corrective/preventive actions initiated and/or completed during the

review period. The APR has a strong link to a firm’s corrective and

preventive action (CAPA) program, and any identified CAPA items

should be tracked appropriately and completed in a timely fashion.

Data Elements

Required. An evaluation of specific data elements, as specified in the

FDA GMP regulations, must be included in the APR:

• Representative number of batches, whether approved or

rejected

• Product complaints

• Recalls

• Returned or salvaged drug products

• Investigations

Expected. In addition to the required data elements, the FDA has

identified, through the issuance of form FDA 483s and other guidance
documents, other data elements that they typically expect to see as

part of the APR:

• Deviations or nonconformances

• In-process and finished product testing results and a discussion

of any adverse trending

• Product stability results and a discussion of any adverse

trending

• Changes to processes that occurred during the review period

In the spirit of continuous improvement, additional data elements may

need to be included in the review process. Firms should assess all of

the data that are gathered throughout their operations and determine

what makes the most sense for their particular products and

processes.