The Ultimate Guide to the FDA’s Current Good Manufacturing Practices (CGMP)

Learn Everything You Need to Know About CGMP Compliance from the FDA Lawyers and Consultants at Oberheiden P.C.

**Attorney Nick Oberheiden**
FDA CGMP Compliance Team Lead

**Attorney Lynette Byrd**
FDA CGMP Compliance Team Lead
Former DOJ Attorney

Attorney John Sellers — **John W. Sellers**
FDA CGMP Compliance Team Lead
Former Senior DOJ Trial Attorney

Pharmaceutical manufacturers that develop drugs and vaccines for sale in the United States—whether domestically or abroad—must comply with the FDA’s Current Good Manufacturing Practices (CGMP). The Current Good Manufacturing Practice regulations are found in the FDA’s regulations promulgated under the Food, Drug, and Cosmetic Act (FDCA); and, for pharmaceutical manufacturers, CGMP compliance is a critical component of an overall FDCA compliance program.

The CGMP are extensive manufacturing processes. As the FDA explains, “[t]he CGMP regulations for drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packing of a drug product.” They are also designed to “make sure that a [pharmaceutical] product is safe for use, and that it has the ingredients and strength it claims to have.” Non-compliance with the CGMP can have various consequences—including, but not limited to, resulting in a prohibition on the sale of an “adulterated” drug and exposing pharmaceutical manufacturers to significant civil monetary penalties (CMP).

CGMP Compliance is Required for Pre-Market Approval (PMA)

While CGMP compliance is important for several reasons, one of the most important reasons from a drug manufacturing perspective is that CGMP compliance is required to secure pre-market approval (PMA) for new drugs. The FDA makes this clear, stating:

“The approval process for new and generic drug marketing applications includes a review of the manufacturer’s compliance with the CGMP. FDA assessors and investigators determine whether the firm has the necessary facilities, equipment, and ability to manufacture the drug it intends to market.”

As a result, pharmaceutical industry manufacturers in the U.S. and abroad need to prioritize CGMP compliance. If failure to comply with the CGMP results in denial of a PMA application, or even in a delay in securing pre-market approval, this can have significant adverse commercial consequences. But, while the CGMP are complex, there are clear guidelines manufacturers can follow; and, with a structured, custom-tailored, and detail-oriented approach, pharmaceutical manufacturers should be able to manage CGMP compliance effectively.

The “Five Ps” of CGMP Compliance

While there are numerous aspects to CGMP compliance, drug companies’ core obligations under the FDA’s CGMP regulations can broadly be divided into five categories. These are commonly known as the “five Ps” of CGMP compliance:

1. Primary Materials and Products

Under the CGMP, pharmaceutical companies must ensure that the primary materials and products (i.e., raw ingredients) they use when manufacturing their drugs meet all applicable CGMP standards for quality assurance. Not only does this require compliant sourcing, but it also requires that companies prevent adulteration and avoid any deviations from their standardized formulas and procedures during the manufacturing process.

2. Premises

The CGMP impose extensive requirements for maintaining reliable testing laboratories and manufacturing facilities. When conducting inspections during the PMA review process, the FDA thoroughly examines all areas and all aspects of manufacturers’ facilities for strict CGMP compliance.

3. People

To effectively manage CGMP compliance, pharmaceutical manufacturers must provide adequate training to all relevant personnel. Not only is this necessary so that employees can do their part to help the company comply with the CGMP’s operational requirements (and identify compliance issues when they arise), but having adequately trained personnel is a specific CGMP requirement as well.

4. Processes

Pharmaceutical manufacturers must implement extensive and detailed processes that are designed to ensure CGMP compliance at all stages of the manufacturing process. Failure to implement (or adhere to) the requirements for process validation is among the most common issues leading to delays in PMA approval; and, process failures uncovered during post-market Food and Drug Administration inspections can lead to injunctions, recalls, revocation of FDA approval, and other costly consequences for manufacturers as well.

5. Procedures

Along with detailed processes, pharmaceutical manufacturers must also implement procedures that are designed to facilitate consistent CGMP compliance. Just like their processes, manufacturers’ procedures must be thoroughly documented, and manufacturers must be prepared to provide this documentation to the FDA during both pre-market and post-market inspections.

5 Key Elements of an Effective CGMP Compliance Program

To effectively address the “five Ps” (in addition to all other necessary aspects of CGMP compliance), drug companies need to develop CGMP compliance programs that are custom-tailored to their operations, facilities, and personnel. To serve its intended purpose, a CGMP compliance program must generally include the following key elements:

1. A Custom-Tailored Approach to CGMP Compliance

The CGMP requirements are extremely broad in scope, touching on essentially all aspects of the drug manufacturing process. But, they also establish different expectations for different companies in many circumstances. As a result, a custom-tailored approach is essential.

2. A Comprehensive Approach to CGMP Compliance

Not only does CGMP compliance require a custom-tailored approach, but it requires a comprehensive approach as well. For example, areas in which pharmaceutical manufacturers must generally address CGMP compliance include (but are not limited to):

Organization and personnel
Buildings and facilities
Laboratory controls
Equipment
Components, containers, and closures
Production and processing
Packaging and labeling
Holding and distribution
Records and reports
Returned and salvaged drug products

When evaluating compliance with the CGMP, the FDA looks for evidence of any violations in any area of a manufacturer’s operations. As even a single violation can have adverse consequences, it is imperative that manufacturers not overlook any applicable regulations under the CGMP.

3. Thorough Documentation of CGMP Compliance (Both Initial and Ongoing)

When conducting inspections, the FDA expects drug companies to be able to provide affirmative demonstrations of their compliance. Among other things, this means that drug companies must have comprehensive compliance documentation on hand. This includes not only documentation of their GMP regulations compliance policies and procedures, but documentation of their ongoing efforts to manage compliance as well.

4. Internal Monitoring, Auditing, Reporting, and Enforcement

To document compliance on an ongoing basis, drug companies must monitor for compliance and conduct internal compliance audits. They must also have systems in place for reporting CGMP-related compliance concerns and for enforcing compliance as warranted.

5. External Monitoring and Engagement with the FDA

Along with internal monitoring, pharmaceutical manufacturers must engage in external monitoring as well. As the FDA explains, “the ‘C’ in CGMP stands for ‘current,’ requiring companies to use technologies and systems that are up-to-date in order to comply with the regulations.” The CGMP regulations (and other FDA-enforced laws and regulations) also change over time. Manufacturers must also know when they need to engage with the FDA as part of meeting their CGMP compliance obligations (or their FDA compliance obligations more broadly), and they must have the systems in place to avoid overlooking applicable application, renewal, reporting, or disclosure obligations.

To be clear, this list is not exhaustive. There are numerous aspects to CGMP compliance, and each manufacturer must develop its compliance policies, procedures, and protocols based on its specific needs At Oberheiden P.C., our lawyers and consultants have extensive experience advising companies regarding the CGMP, and we rely on this experience to help all of our clients effectively manage CGMP compliance on an ongoing basis.

Dr. Nick Oberheiden

Founder

Attorney-at-Law

Lynette S. Byrd

Former DOJ Trial Attorney

Partner

Brian J. Kuester

Former U.S. Attorney

Hon. Kevin McCarthy

55th Speaker, U.S. House of Representatives (ret.)

Government Consultant

Mike Pompeo

Of Counsel

Former U.S. Secretary of State

John W. Sellers

Former Senior DOJ Trial Attorney

Linda Julin McNamara

Federal Appeals Attorney

Nicholas B. Johnson

Former Prosecutor

Roger Bach

Former Special Agent (DOJ)

Chris J. Quick

Former Special Agent (FBI & IRS-CI)

Michael S. Koslow

Former Supervisory Special Agent (DOD-OIG)

Ray Yuen

Former Supervisory Special Agent (FBI)

FAQs: Managing an Effective CGMP Compliance Program

When Is CGMP Compliance Required?

The FDA’s Current Good Manufacturing Practices apply to drug companies. As the FDA explains, “[i]f a company is not complying with CGMP regulations, any drug it makes is considered ‘adulterated’ under the law.” Since selling adulterated drugs violates the Food, Drug, and Cosmetic Act (FDCA), CGMP compliance is required for all drugs manufactured and/or sold in the United States.

What Do the CGMP Require?

The CGMP require that drug companies undertake extensive efforts to ensure that their products are of a consistent formula and quality, are unadulterated, and are properly stored and packaged. To meet these requirements, drug companies must implement exhaustive processes and procedures in all aspects of their operations, from how they manage their facilities to how they train their personnel. Drug companies must document their CGMP compliance efforts as well, as compliance is required to secure pre-market approval from the FDA.

What Does it Take to Effectively Manage CGMP Compliance?

Effectively managing CGMP compliance requires a top-down commitment to addressing all pertinent obligations under the FDA’s regulations. As even minor oversights can have significant consequences for drug manufacturers, it is imperative that manufacturers work with experienced counsel to ensure that they are consistently doing what is necessary on an ongoing basis.

What Are the Risks of Non-Compliance with the CGMP?

Non-compliance with the CGMP presents several risks for pharmaceutical manufacturers. Along with denial of their pre-market approval (PMA) applications, non-compliant manufacturers can also face fines, mandatory corrective action plans, recalls, revocation of approval, and other consequences.

Do You Need Outside Counsel to Effectively Manage CGMP Compliance?

Due to the complexity of the CGMP and the potential ramifications of non-compliance, engaging experienced outside counsel will be necessary for most companies. At Oberheiden P.C., we have extensive experience helping companies comply with the CGMP, and our lawyers and consultants can help your company implement a comprehensive and custom-tailored CGMP compliance program.

Contact the FDA Compliance Lawyers and Consultants at Oberheiden P.C.

If you would like to know more about our CGMP compliance services, we invite you to get in touch. Please call 888-680-1745 or contact us online to schedule a complimentary consultation with a member of our FDA compliance team today.