FDA Publishes Guidance for the Production of Medically Necessary Drugs

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ePT--the Electronic Newsletter of Pharmaceutical Technology

The US Food and Drug Administration published a guidance last week intended to ensure the availability of medically necessary drug products during emergencies.

The US Food and Drug Administration published a guidance last week that is intended to ensure the availability of medically necessary drug products (MNPs) during emergencies such as an influenza pandemic. The guidance cites the Center for Drug Evaluation and Research’s (CDER’s) definition of a medically necessary drug product as any drug used to treat or prevent a serious disease for which no appropriate substitute is adequately available.

FDA encourages the makers of MNPs to draft contingency production plans before an emergency situation occurs so that these products can be produced during periods of high absenteeism at production facilities. Manufacturers of finished drug products also should “coordinate their suppliers’ and contractors’ responses to personnel shortages to ensure the availability of high-quality materials and services that contribute to the manufacture of MNPs,” according to the guidance.

The guidance offers advice about how plans should be drafted and what they should address. In accordance with the requirements in 21 CFR 211.100(a) and 211.160(a), pharmaceutical companies should develop, write, review, and approve their plans within their sites’ change-control quality systems. A plan should address the specific conditions of each location where it is to be implemented, says the guidance. CDER observes that a company could develop a plan for each individual manufacturing facility and a more general plan that covers various sites within the organization.

Firms that expect many employees to be absent should prioritize MNPs when they schedule manufacturing and make plans for reassigning or cross training personnel, says the guidance. A company should give special focus to MNPs for which it is sole source or for which it supplies a significant share of the US market.

In the guidance, CDER recommends companies that anticipate a high rate of absenteeism that could affect the production of MNPs to take the following measures:
• Increase inventory of MNPs
• Increase inventory of components needed for the manufacture of MNPs
• Conduct cross-training exercises to ensure the competency of personnel that might be reassigned to the manufacture of MNPs
• Perform maintenance, calibrations, and other activities that take place periodically so that these activities are not scheduled to occur during an active emergency plan
• Establish competent resources at alternate sites, including contractors (e.g., qualified testing labs or manufacturing equipment)
• Find alternative suppliers of goods and services, including distributors, based on the suppliers’ projected absenteeism rates.


When developing a plan to address high rates of absenteeism, a company should conduct a risk assessment of its processes so that the plan will help meet the demand for MNPs, provide a high level of assurance that the manufacturer complies with current good manufacturing practices (CGMPs), and ensure that products meet specifications. CDER recommends that if the primary measures it proposes to address production of all MNPs are insufficient, manufacturers “apply quality risk assessments to identify activities that might be reduced in frequency, delayed, or substituted by a suitable alternative.” The guidance cautions that reductions should be based on well-supported conclusions and process and product knowledge.

In the guidance, CDER recognizes that, even if a drugmaker’s emergency plan is activated, an emergency might lead to the manufacture of MNPs that do not meet all statutory and regulatory requirements. “CDER is prepared to exercise enforcement discretion in such cases as appropriate to meet the national public health needs so long as the product remains safe and effective,” FDA says in the guidance.

CDER recommends that manufacturers take preventative measures in addition to developing emergency plans. Preventative measures can include educating employees about personal hygiene and the appropriate use of sick leave, ensuring that employees are immunized, reviewing CGMP regulations regarding appropriate sanitation practices, and restricting ill or sick employees’ access to production areas.

In addition, CDER encourages manufacturers to include a procedure in their plans for notifying CDER when the plan is activated and when returning to normal operations. “These communications are intended to help CDER maintain awareness of any potential shortage situations and act accordingly to avoid or mitigate them,” says the guidance.