Client Project- Pharmaceutical Company Alignment with Combination Product and Device CGMP
In July 2013, the United States Food and Drug Administration (FDA) instigated a new regulation Current Good Manufacturing Practice (CGMP), which has significant implications for pharmaceutical and device manufacturers. Even if a company is best in industry for CGMP, the requirements apply when drugs, devices, and biological products are combined to create a combination product.
Ultimately, the CGMP alignment requires a paradigm shift in how pharmaceutical companies think about products. Although a syringe may have been previously thought as separate from the drug product, the FDA regulations now consider the product as a combination product. Thus, a new mindset is necessary, recognizing that many companies are now device manufacturers as well as drug manufacturers.
What is a Combination Product?
A combination product is a product that consists of two or more different products: a drug and a device, a biological product and a device, a drug and a biological product, or a drug, device, and a biological product. According to 21 CFR 3.2(e), a combination product is defined as:
- A product comprised of two or more regulated components (i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic) that are physically, chemically, or otherwise combined or mixed and produced as a single entity;
- Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;
- A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where, upon approval of the proposed product, the labeling of the approved product would need to be changed (e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose); or
- Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.
Alignment with current FDA regulations is thereby necessary to prevent a violation of the Federal Food, Drug, and Cosmetic Act. Thus, it is critical for companies to understand the regulation as it relates to the Pharmaceutical Quality System (PQS), because the existing operating procedures need to incorporate additional elements that are unique to medical devices.
Gap identification in the Pharmaceutical Quality System, compared with FDA regulatory requirements for Combination Product CGMP
At Enterey, we understand that implementing changes to an existing Quality System requires planning, time, and expertise. To avoid Health Authority action due to non-compliance, and to establish a PQS that is appropriate for the development and manufacture of combination products and constituent parts, a pharmaceutical company needs to fully assess current operating procedures in the context of the new FDA regulatory requirements. Subsequently, a transparent risk-based Quality System gap assessment determines the overall strategy to fill the gaps between the CGMP and the PQS. Depending on the high-risk focus areas, especially noting a review of purchasing controls (21CFR820.50), workstreams should be developed with the overall goal to incorporate key elements of the device regulations into the global Pharmaceutical Quality System.
To ensure full compliance with the FDA requirements as they relate to combination products and constituent parts, a company needs to implement the appropriate changes in an efficient and timely manner. A successful gap identification and remediation strategy promotes a reliable manufacturing process, which creates a harmonized global Pharmaceutical Quality System that is compliant with current Health Authority regulations. At Enterey, we find that filling the gaps not only includes supplemental Standard Operating Procedures (SOPs), but also changes the company mindset to ensure employees are trained on the rationale behind the new processes. Ultimately, the change in organizational mindset will support the incorporation and maintenance of device requirements across all documents, processes, and systems, and ensure a successful pipeline with the manufacture of a reliable product for the patient.
For inquiries on how this might apply to your business, call Enterey (800) 691-2349.