Zachary S. Anderson is global market segment lead—Sterility Assurance, Nelson Laboratories.

Zachary S. Anderson 

Question mark background | Image Credit: © Leigh-Prather - © Leigh Prather - stock.adobe.com

Q: I am evaluating a new contract development and manufacturing organization (CDMO) to manufacture some of our injectable products. Can you advise on some of the elements of their environmental monitoring (EM) program I should review, so I can ascertain its suitability?

A: Evaluating the suitability of an environmental monitoring program can be complicated. The evaluator needs to understand the multi-layered elements required for the successful and sustainable management of the EM program. Fundamentally, it is important to be familiar with the regulations that govern the manufacture of injectable products. FDA and the European Medicines Agency (EMA) have regulations that outline these expectations (1,2). The revised Annex 1 guideline introduces the concept of contamination control strategy (CCS) by stating. “A [CCS] should be implemented across the facility to define all critical control points and assess the effectiveness of all the controls (design, procedural, technical, and organizational) and monitoring measures employed to manage risks to medicinal product quality and safety. The combined strategy of the CCS should establish robust assurance of contamination prevention” (2). The guideline also states, “The CCS should consider all aspects of contamination control with ongoing and periodic review resulting in updates within the pharmaceutical quality system as appropriate. Changes to the systems in place should be assessed for any impact on the CCS before and after implementation” (2). The 2004 FDA guidance states, “Any manual or mechanical manipulation of the sterilized drug, components, containers, or closures prior to or during aseptic assembly poses the risk of contamination and thus necessitates careful control” (1).

One of the first steps in the assessment would be to evaluate the manufacturer’s CCS based on the expectations outlined in the regulations.

Using the CCS as a guide, the assessor can then focus on specific elements of the EM program as well as how the program is embedded into the quality management system (QMS). The following are questions to ask to help in the evaluation:

QMS: Is the EM program effectively integrated into the QMS, including corrective action and preventive action (CAPA) program that drives to root cause?

Technical expertise: Has the company hired experienced personnel and demonstrated maintenance of expertise? What are the ongoing training requirements for personnel in Quality Assurance, the laboratory and on the manufacturing floor? Are gowning requirements for all personnel who enter the manufacturing area documented? Are the re-qualification requirements for gowning clearly defined? Is the out-of-specification procedure understood and followed? Are employees trained on data recording and integrity? Does the program drive the recording of the appropriate level of detail?

Process controls. Are process controls for particulates and microbiological organisms robust enough to detect and manage changes in practice or gaps in process (e.g., data lags, emerging issues/environment degradation, product quality shifts, etc.)?

There are many more questions that should be asked to ascertain the suitability of an environmental monitoring program than listed above. The optimal way to approach such an evaluation is to become familiar with the regulations, review the company’s CCS program and drill down into specific areas of the program by asking targeted questions. Inevitably, you will encounter variations and “gray-area” interpretations. An astute evaluator will ensure variations are acknowledged (documented) and interpretations are justified in writing. Asking why things are done a certain way will help make an accurate assessment of an organizations EM program and help determine whether it suits your requirements.

Guidance for Industry, Sterile Drug Products Produced by Aseptic Processing–Current Good Manufacturing Practice

Guidelines for Good Manufacturing Practice Medicinal Products for Human and Veterinary Use

, Annex 1: Manufacture of Sterile Medicinal Products (EC, 2022 rev.).

Susan Schniepp is distinguished fellow at Regulatory Compliance Associates. Zachary S. Anderson is global market segment lead—Sterility Assurance, Nelson Laboratories.

When referring to this article, please cite it as Schniepp, S. and Anderson, Z.S. Elements for a Sustainable Environmental Monitoring Program. 

Articles

Asking why things are done a certain way will help make an accurate assessment of an organization’s EM program, says Susan Schniepp, distinguished fellow at Regulatory Compliance Associates, and Zachary S. Anderson, global market segment lead—Sterility Assurance, Nelson Laboratories.