Regulatory Series | Fundamental Guideline for GMP Standards: ICH Q7 Guideline

Regulatory Series | Fundamental Guideline for GMP Standards: ICH Q7 Guideline

Written By: Akshaya Mohan, Regulatory Affairs Manager, PSC Biotech®

Quality lies at the heart of every pharmaceutical process. You build quality into your product! Current Good Manufacturing Practices (cGMPs) are the minimum legal requirements to assure the quality of your pharmaceutical product.  While companies can test the final product to check for quality specifications, testing is just a check and does not substitute for quality is built into every step of the process.

You can’t test a Volkswagen into a Cadillac!  If you want to build a Cadillac you plan, design, and build a Cadillac.  You manufacture your quality pharmaceutical product by building quality into every stage of the product life cycle, from the R&D stage through the manufacturing, storage and distribution until the product reaches the end user.  When you build quality in, you get quality products out of your process.

The ICH Q7 guideline

The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) was founded by three Regulatory Agencies with the objective of harmonizing standards and regulations across countries and ensure consistency of the drug product and reduce duplication of efforts. Today, ICH guidelines are one of the most widely followed guidelines and accepted in many countries.

The ICH Q7 guideline focuses on how cGMP practices can be implemented for the manufacturing of Active Pharmaceutical Ingredient (API) or the active drug substance. While ICH Q7 formally applies to manufacturing of APIs, ICH Q7 can also be a good starting point for companies manufacturing any kind of product to bring cGMPs into their processes.

Key elements of ICH Q7 include:

1. Quality Management System: Companies need to establish quality units responsible for ensuring quality, developing and monitoring production activities as well as performing periodic internal audits and quality reviews.

2. Personnel: Your personnel need appropriate training, education, and experience to do their assigned jobs. You need to document personnel training.

 

ICH Q7

3. Buildings and Facilities: You need proper buildings, equipment, and utilities.  You need to validate and maintain your physical assets.

4. Process Equipment: You need to ensure that all your equipment is designed as per required specifications, that they are cleaned and maintained properly, as well as calibrated, validated, and periodically revalidated.

5. Documentation and Records: In the life-science industry “If it isn’t documented, it didn’t happen”. Good Documentation Practices (GDP) are how you prove it happened. You need to ensure all processes are documented clearly in simple language and indicate the latest practices, retain documents, and establish electronic database systems that can maintain an audit trail, track changes and deviations to aid in inspections.

6. Materials Management: You need procedures for receipt, identification of materials as well as their storage, handling, sampling, testing and rejection.

7. Production and Process Controls: You need in-process controls, acceptance criteria, contamination controls, etc.

8. Packaging and Labeling: You need procedures and controls for Packaging and Labeling materials and operations.

9. Storage and Distribution: You need procedures and controls for storage, shipping, and distribution. If you had to recall the product, does your system tell you quickly where it went?  Do you test your systems?

While this is not an exhaustive list of CGMP systems and processes you need, consult ICH Q7 Guideline at https://www.ich.org/page/quality-guidelines  as well as your local Regulatory Agency’s laws, regulations, and guidance documents.

PSC Biotech® offers professional services such as Quality Assurance and Support, Commissioning and Decommissioning services, Validation services, Regulatory Affairs support, Audit functions as well as Engineering support that can help your company implement the latest cGMPs for your processes to meet ICH and all the other regulations you have to comply with.

Contact us today if you need support with any of these services to help you accelerate your success!

How Poor Compliance Impacts Your Bottom Line

How Poor Compliance Impacts Your Bottom Line

Written By: Akshaya Mohan, Regulatory Affairs Manager, PSC Biotech®

Life science companies need to comply with laws, regulations, and Agency guidance.  Compliance requires understanding processes and technologies and ensuring that quality is built into your process and product.  Compliance means you have the documentation that proves the quality of your product and processes.  When you have compliance issues, you spend your time and your money fixing them, raising your costs and lowering your output.

The figure below shows FDA 483 citations related to various quality and compliance issues.   

®Key compliance issues observed in 2020 include the following.

  • Absence of written procedures and clear SOPs (21 CFR Part 211): This is most observed compliance issue. Specific compliance deficiencies include lack of written procedures, ambiguity with respect to roles and responsibilities assigned, complex language in SOPs, failure to timely update SOPs, and lack of proper description of the steps in the operations.
  • Improper Data Management (21 CFR Part 11): This compliance failure relates to lack of proper data systems that can appropriately use, store, retrieve or archive data efficiently. You need to develop and maintain data management systems that properly manage and control your data.
  • Lack of control procedures (21 CFR Part 211): Another common issues is inadequate control procedures, whether the absence of control of control procedures for batch controls, in-process controls, laboratory controls, labelling control, etc.
  • Inadequate Cleaning, Sanitization, problem of cross contamination (21 CFR Part 211.67): You need to maintain proper procedures for cleaning and sanitization. Inadequate cleaning protocols can be a direct cause of contamination.  You also need to prevent cross contamination from other products or raw materials in production and storage areas and holding areas for active pharmaceutical ingredients, intermediates, finished drug products and container closure systems.

Procedures are just one part of compliance.  Procedures don’t work by themselves.  You need personnel trained for the specific operations.

Companies with strong quality compliant procedures, documentation, and trained personnel consistently achieve the highest compliance to laws, regulations and guidance’s and produce products with the highest quality, safety and efficacy.

PSC Biotech® offers an array of professional services, including Quality Assurance and Compliance Gap Assessment and Remediation, Auditing, Calibration, Technical Writing for procedures and SOPs, and Regulatory Affairs advice.  PSC’s® software solutions such as ACE® (Adaptive Compliance Engine®) and ACE Essentials™ are fully integrated, validated, centralized electronic Quality Management Systems that have been in use by various life- science companies to manage essential aspects of quality systems and ensure compliance.

Call us today to explore the right solution for your needs.

References:

  • 21 CFR (Code of Federal Regulations) Part 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals), Part 210 (Current Good manufacturing practices in manufacturing, processing, packing and holding of drugs), Part 11 (Electronic Records: Electronic Signatures), Part 820 (Quality System Regulation)
  • Annex 5, World Health Organization, Guidance on good data and record management practices
  • ICH Q7 guideline: Good Manufacturing practices for Active Pharmaceutical Ingredients
FDA Combination Products Q&A

FDA Combination Products Q&A

Written By: Jorge Sugranes, Regional Director of Latin America, PSC Biotech

Here are some Q&A regarding combination products (CP) that you might like. I found this information, published by the FDA*, very helpful, educational, and clarifies common questions about CP.

*Reference: fda.gov

How are combination products assigned for review?

Combination products are assigned to FDA center that will have primary jurisdiction for its premarket review and regulation. Consistent with section 503(g)(1) of the Act, assignment to a center with primary jurisdiction for premarket review and post-market regulation, or a lead center, is based on a determination of the “primary mode of action” (PMOA) of the combination product. For example, if the PMOA of device-biological combination product is attributable to the biological product, the Agency component responsible for premarket review of that biological product would have primary jurisdiction for the combination product.

Section 503(g) defines primary mode of action as “the single mode of action of combination product that provides the most important therapeutic action of the combination product” (see also definitions at

2 CFR 3.2. In some cases, the most important therapeutic action cannot be determined. For example, combination product may have two independent modes of action, neither of which is subordinate to

the other. To resolve these types of questions, FDA’s regulations at 2 CFR Part 3 include an algorithm for determining center assignment. The algorithm directs center assignment based on which center regulates combination products raising similar types of safety and effectiveness questions, or, if there is n such center, based o which center has the most expertise to evaluate the most significant safety and effectiveness questions raised by the combination product.

What is the process for obtaining an Agency decision regarding the classification or center assignment for my medical product?

Sponsors may request formal assignment through the Request for Designation (RFD) process or alternatively obtain informal non-binding feedback regarding their combination product or product through submission of a Pre-Request for Designation (Pre-RFD).

 

How do I submit a Pre-Request for Designation (Pre-RFD)?

The Pre-RFD process is available to provide informal, non-binding feedback o whether a medical product is a drug, device, biological product, or combination product and/or the Center to which it would be assigned. Sponsors may contact OCP (i.e. at combination@fda.gov for information about how to submit a Pre-RFD. Additionally, OCP recently published a draft guidance about Pre-RFDs that may be helpful.

What types of marketing applications are required for a combination product?

Combination products are typically marketed under a marketing authorization type associated with the constituent part that provides the primary mode of action (PMOA) for the combination product (i.e., a new drug application (NDA) or abbreviated new drug application (ANDA) if it has a drug PMOA, a biologic license application (BLA) if it has a biologic PMOA, or a premarket approval application (PMA), de novo classification, or premarket notification (“510(k)”) if it has a device PMOA). A single marketing application is generally sufficient for combination product. In some cases, however, a sponsor may wish to submit separate marketing applications for different constituent parts of a combination product, and FDA may consider this permissible.

FDA
Quality Assurance (QA), Quality Control (QC) and Industry 4.0

Quality Assurance (QA), Quality Control (QC) and Industry 4.0

Written by: Shauna Clizbe, Business Development Manager

The biomanufacturing industry is currently undergoing a revolution in how it develops products. This paradigm shift is known as Industry 4.0. Industry 4.0 focuses on how to apply predictive modeling, data, analytics, artificial intelligence, and automation technology for the Digital Transformation of biomanufacturing manufacturing. 

Companies are investing in improved analytics, process control, and more of the elements of Industry 4.0.  Examples include using data and analytics from raw materials and bioproduction operations to improve the process with the goals of improving efficiency, lowering costs, and getting products to market faster. Quality Assurance (QA) and Quality Control (QC) are of utmost importance in the production of API’s, pharmaceuticals, and biopharmaceutical products, not just to meet Good Manufacturing Practices (cGMP) standards and regulatory requirements, but as a major tool in the Digital Transformation.  Processes and controls must be effective and enforced throughout your facility and process, from clean room operations to calibration of instruments and preventative maintenance in utilities systems.
Quality Control
While investing in better automation and analytics, biopharma manufacturers can take advantage of modular, pre-validated, and pre-tested single-use equipment, bioreactors, and chromatography systems that include built in electronic batch record (EBR) and manufacturing execution system (MES) functionality.  Integration of these complex systems with a QC and QA team can be a complex and sometimes difficult task.  Quality Control and Quality Assurance play inter-related and essential roles.  Creating successful QC and QA programs within the organizations can be streamlined by following some best practices;

  • Train your staff;
  • Documentation is key, especially in the age of Industry 4.0;
  • Perform at least an annual review of SOPs, policies, and programs;
  • QA and QC must enable your efforts, not disable them;

Be independent of the rest of the organization;

Creating QC and QA programs in any regulated industry is essential for success; contact PSC Biotech to learn about our Quality Services and Programs today!

What is Gap Analysis and how is it conducted?

What is Gap Analysis and how is it conducted?

What is Gap Analysis?

Gap Analyses is the systematic, documented review of an organization’s current state to identify gaps or opportunities for continuous improvement in “whatever”, be it quality systems, corporate governance, process optimization, operational efficiency, internal audit, or financial reporting. Biotechnology, Life Sciences and Healthcare organizations conduct gap analyses as a part of their continuous improvement programs.

What do Gap Analyses tell us?

Gap analyses tells you what you are doing now, how it compares to the current state-of-the-art, and what you need to do to bring your practices up to the current Good Practice used in your industry.  You and your team work to close these ‘gaps’ and improve your systems and efficiency.

How is Gap Analysis conducted?

Audit companies conduct gap analyses in five phases;

Phase 1 – Planning and Preparation

This is the phase where the scope of analysis, problems, goals, and tasks are planned out. A gap analysis questionnaire is formulated along with the content, format, and schedule to conduct the gap analysis.

Phase 2 – Reviewing Background Information

In this phase, we review documents, reports, and evidence.

Phase 3 – Interviews with Stakeholders

Managers, process owners, service managers, and management personnel are interviewed in this phase. The interviews are based on the questionnaire prepared in Phase-1 of the analysis planning. This is crucial to identify and establish problems, inefficiencies and a common consensus about the goals that need to be achieved post the gap analysis, and possible solutions.

Phase 4 – Review of Draft Gap Analysis

In this phase, the stakeholders, teams and other personnel can review the result of the analyses from previous phases. It is the final step whereby the stakeholders can ensure that all the gaps have been included and nothing is missing in the draft Gap Analysis.

Phase 5 – Delivery of Final Formal Report

The final formal report contains the findings within the processes, systems and patterns of operation of the organization. Here, the stakeholders can add notes in the formal report to include the recommendations for short, medium, and long-term goals to make your gaps “disappear”.

Need a gap analyses audit expert? Contact PSC Biotech for cutting-edge quality engineer gap analysis expertise.

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