QUALITY SYSTEMS MODEL
The goal is to describe a model for use in pharmaceutical manufacturing that can help manufacturers comply with the CGMP regulations. It should be noted that implementing an effective quality system in a manufacturing organization will require a significant investment of time and resources. However, we believe the long-term benefits of implementing a quality system will outweigh the costs.
The model is described according to four major factors:
- Management Responsibilities
- Manufacturing Operations
- Evaluation Activities
In each of the sections that follow, the specific elements of a robust modern quality systems model are described. When elements of the quality systems model correlate with specific CGMP regulations, this correlation is noted.
Appropriate allocation of resources is key to creating a robust quality system and complying with the CGMP regulations. This section discusses the role of resources in developing, implementing and managing a robust quality system that complies with the CGMP regulations.
1. General Arrangements
Under a robust quality system, sufficient resources should be allocated for quality system and operational activities. Under the model, senior management, or a designee, should be responsible for providing adequate resources for the following:
To supply and maintain the appropriate facilities and equipment to consistently manufacture a quality product
To acquire and receive materials that are suitable for their intended purpose
For processing the materials to produce the finished drug product
For laboratory analysis of the finished drug product, including collection, storage, and examination of in-process, stability, and reserve samples
2. Personnel Development
Under a quality system, senior management should support a problem-solving and communicative organizational culture. Managers should encourage communication by creating an environment that values employee suggestions and acts on suggestions for improvement. Management should also develop cross-functional groups to share ideas to improve procedures and processes.
In a quality system, personnel should be qualified to do the operations that are assigned to them in accordance with the nature of, and potential risk of, their operational activities. Under a quality system, managers should define appropriate qualifications for each position to help ensure that individuals are assigned appropriate responsibilities. Personnel should also understand the effect of their activities on the product and the customer. Although QU personnel should not take on the responsibilities of other units of the organization, these personnel should
be selected based on their scientific and technical understanding, product knowledge, process knowledge and/or risk assessment abilities to appropriately execute certain quality functions (this quality systems feature is also found in the CGMP regulations, which identify specific qualifications, such as education, training, and experience or any combination thereof (see § 211.25(a) and (b)).
Under a quality system, continued training is critical to ensure that the employees remain proficient in their operational functions and in their understanding of CGMP regulations. Typical quality systems training should address the policies, processes, procedures, and written instructions related to operational activities, the product/service, the quality system, and the desired work culture (e.g., team building, communication, change, behavior). Under a quality system (and the CGMP regulations), training should focus on both the employees’ specific job functions and the related CGMP regulatory requirements.
Under a quality system, managers are expected to establish training programs that include the following:
Evaluation of training needs
Provision of training to satisfy these needs
Evaluation of effectiveness of training
Documentation of training and/or re-training
When operating in a robust quality system environment, it is important that managers verify that skills gained from training are implemented in day-to-day performance.
3. Facilities and Equipment
Under a quality system, the technical experts (e.g., engineers, development scientists), who have an understanding of pharmaceutical science, risk factors, and manufacturing processes related to the product, are responsible for defining specific facility and equipment requirements
Under the CGMP regulations, the quality unit ( QU) has the responsibility of reviewing and approving all initial design criteria and procedures pertaining to facilities and equipment and any subsequent changes (§ 211.22(c)).
Under the CGMP regulations, equipment must be qualified, calibrated, cleaned, and maintained to prevent contamination and mix-ups (§§ 211.63, 211.67, 211.68).
Note that the CGMP regulations require a higher standard for calibration and maintenance than most nonpharmaceutical quality system models. The CGMP regulations place as much emphasis on process equipment as on testing equipment (§§ 211.160, 211.63, 211.67, and 211.68) while most quality systems focus only on testing equipment.11
4. Control Outsourced Operations
Outsourcing involves hiring a second party under a contract to perform the operational processes that are part of a manufacturer’s inherent responsibilities. For example, a manufacturer may hire another firm to package and label or perform CGMP regulatory training. Quality systems call for contracts (quality agreements) that clearly describe the materials or service, quality specification responsibilities, and communication mechanisms.
Under a quality system, the manufacturer should ensure that a contract firm is qualified before signing a contract with that firm. The contract firm’s personnel should be adequately trained and monitored for performance according to their quality system, and the contract firm’s and contracting manufacturer’s quality standards should not conflict. It is critical in a quality system to ensure that the management of the contractor be familiar with the specific requirements of the contract.
However, under the CGMP requirements, the manufacturer’s QU is responsible for approving or rejecting products or services provided under a contract (§ 211.22(a)).
As the following table illustrates, the CGMP regulations are consistent with the elements of a quality system in many areas in this section. However, manufacturers should always refer to the specific regulations to ensure that they are complying with all regulations.
|21 CFR CGMP Regulations Related to Resources|
|1. General Arrangements||—|
|2. Develop Personnel||Qualifications: § 211.25(a)|
|Staff number: § 211.25(c)|
|Staff training: § 211.25(a-b)|
|3. Facilities and Equipment||Buildings and facilities: §§ 211.22(b), 211.28(c),
211.42 – 211.58, 211.173
|Equipment: §§ 211.63 – 211.72, 211.105, 211.160(b)(4),
|Lab facilities: § 211.22(b)|
|4. Control Outsourced Operations||Consultants: § 211.34|
|Outsourcing: § 211.22(a)|
Reference: Guidance for Industry -Quality Systems Approach to Pharmaceutical CGMP Regulations
Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field.
During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube