GMP Compliance for Pharmaceutical Laboratories

GMP Compliance for Pharmaceutical Laboratories

Key Takeaway:

In order to ensure GMP compliance, pharmaceutical laboratories have to devise a holistic and long term plan that covers all aspects of the laboratory’s activities.

Good Manufacturing Practices (GMP) requirements for laboratories have been set out by various regulatory bodies. The aim of GMP compliance for a pharmaceutical laboratory is to ensure that

• Products must meet high quality standards consistently
• They should fulfil their intended use
• Policymaking
• They must be compliant with the requirements set out in the Marketing Authorization (MA) or product specification

Result of guidelines from various regulatory authorities

Guidelines for GMP compliance for pharmaceutical laboratories are issued in conjunction with related regulations and guidelines. Some of these are

• ICH, consisting of guidance documents of respective member countries, numbered as Q7, Q8, Q9 and Q3D
• PIC/S: Pharmaceutical Inspection Convention/Cooperation Scheme
• GMP regulations of EU and the US
• European and US pharmacopeias, with suggestions on implementing USP regulations such as 1058, 1224, 1226, 232/233

GMP compliance for a pharmaceutical laboratory consists of

In essence, we can understand the core of FDA Medical Device GMP Guidelines to mean the

The next important stage in ensuring compliance across all workflow steps consists of compliance across all workflow steps. These include

To make GMP compliance for a pharmaceutical laboratory comprehensive, the laboratory should put in place a comprehensive compliance master plan, which

More learning can be had on this topic at (http://www.globalcompliancepanel.com)

A sound Food Safety Management System is an imperative in today’s globalized food supply chain

A sound Food Safety Management System is an imperative in today’s globalized food supply chain

Key Takeaway:

A food safety management system is absolutely necessary for ensuring public health. This is all the more important in today’s globalized world, in which food knows no national borders or boundaries.

First, let us get an understanding of Food Safety Management System or FSMS. Food Safety Management System may be described as a network of interrelated components that fuse and synchronize in ensuring that food is prepared and consumed safely without causing adverse health effects on humans.

Governments and organizations from all over the world coordinate with multifold agencies over several programs to ensure this. Steps for ensuring that a proper Food Safety Management System is put in place include these among many others:

• Planning
• Policymaking
• Setting out guidelines for procedures, processes and practices.

Such a coordinated action plan could also include accomplishing set goals and objectives and the methods to be adopted to get there. A lot of documents and record go into this.

Key Elements of a Food Safety Management System

A well laid out Food Safety Management System usually consists of these five basic key elements:

In essence, we can understand the core of FDA Medical Device GMP Guidelines to mean the

All these are done to ensure the manufacture, storage, packaging, distribution and sale of safe food. To strengthen these, Food Safety Management Systems have programs, accreditations and certifications to ensure that food quality is verifiable and measurable. Some of the present global standards include:

A brief look into the nature of FDA medical device GMP guidelines

Key Takeaway:

The FDA’s guidelines on medical devices GMP regulations are broad and flexible. The onus of proving compliance with the guidelines in accordance with appropriate sections of part 820 lies with the manufacturer.

The FDA has issued Good Manufacturing Guidelines for medical devices. This is necessary since medical devices constitute one of the major areas of FDA regulation. The preamble of FDA’s Quality System (QS) regulation or what it calls the Medical Device Good Manufacturing Practices states that “Manufacturers must establish and follow quality systems to help ensure that their products consistently meet applicable requirements and specifications”.

Quality Systems for medical devices are known as Current Good Manufacturing Practices (cGMPs) and are codified under part 820. They are currently bunched together along with the following:

• Foods
• Drugs, and
• Biologicals

Broad and flexible guidelines

The QS regulation for FDA Medical Device GMP Guidelines follows what is called an “umbrella” approach to the cGMP regulation. What this means is that a broad set of regulations applies to a variety of medical devices. The reasoning for this approach is that the regulation must apply to several different types of devices. This being the case, it is almost impossible to prescribe cGMP regulations for each of these, as each manufacturer will have unique aspects built into a device it manufactures.

In essence, we can understand the core of FDA Medical Device GMP Guidelines to mean the

A brief understanding of the FDA General Principles on Process Validation

A brief understanding of the FDA General Principles on Process Validation

Key Takeaway:

The FDA has issued vastly improved and expanded general principles on process validation in January 2011. These build substantially on the previous issue of 1987.

The FDA describes Process Validation as “the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products”.

Being a regulatory body, the FDA has assigned to itself the task of issuing guidelines to the industry on the principles of process validation (PV). FDA general principles on process validation, the latest of which were issued in 2011 replacing those of 1987, are aimed at facilitating:

• Modern manufacturing principles
• Sound science
• Risk assessment and mitigation
• Process improvement
• Innovation

Basis to the FDA general principles

FDA general principles on process validation are founded on the understanding of the following conditions:

How should product quality be ensured according to the FDA general principles on process validation?

FDA general principles on process validation of 2011 lay clear emphasis on the requirement of Quality. Accordingly, a product should show quality performance consistently in every batch and every unit.

What about PV?

Likewise, the FDA general principles on process validation tie process validation to the product lifecycle approach. In a nutshell, the lifecycle approach to PV binds product and process development to the commercial manufacturing process, and requires the process to be maintained in a state of control during routine production. The FDA believes that:

• Validation is a journey, not a destination
• Commercial production throws up more and more knowledge of PV
• In order to comprehend sources of variability and achieve an understanding of process; there is a need for comprehensive process design
• Risk management has to be built into process validation

The Three Stages of PV

According to the FDA general principles on process validation, Process Validation consists of three stages:

Implementation of FDA 21 CFR Part 11 Regulations optimizes an organization’s capabilities

Implementation of FDA 21 CFR Part 11 Regulations optimizes an organization’s capabilities

Key Takeaway:

On the surface, FDA 21 CFR Part 11 regulations appear confusing, but following a risk based approach to computer systems validation sorts these out, increases the organization’s computer systems efficiency and reduces costs

FDA 21 CFR Part 11 regulations have been codified to ensure that companies implement good business practices into their computer systems. Implementation of FDA 21 CFR Part 11 regulations into an organization’s computer systems is a sure way of enhancing the efficiency of employees, identifying risks and thereby reducing errors, and thus increasing the productivity in the organization.

Outstanding features of FDA 21 CFR Part 11 regulations

Before the advent of electronic records and approval signatures; these were being done on paper. The purpose of FDA 21 CFR Part 11 regulations is to ensure that an electronic record that replaces a paper record and an electronic signature that replaces a handwritten signature have to be authenticated. Regulatory authorities have to be convinced that these digital formats are as authentic and trustworthy as the physical ones they replace.

• FDA 21 CFR Part 11 regulations are part of the Code of Federal Regulations (CFR)
• CFR contains laws that each government agency has to fulfill
• The CFR has several titles, and each of these addresses a designated, regulated area
• Critical areas of laws under the CFR relate to electronic records and approval signatures.

Three primary areas of 21 CFR Part 11 compliance

Compliance with 21 CFR Part 11 regulations consists of three core areas:

FDA 21 CFR Part 11 Compliance

FDA 21 CFR Part 11 Compliance

Key Takeaway:

FDA 21 CFR Part 11 Compliance sets out benchmarks by which FDA-regulated industries’ electronic signatures and other records are considered authentic. From 2007, a strong body of opinion has emerged challenging the stringency of these requirements, but nothing major has been diluted from these.

The regulations under FDA 21 CFR Part 11 Compliance set out criteria that the Food and Drug Agency (FDA) considers in order to deem electronic signatures authentic. The electronic records, electronic signatures, and handwritten signatures executed to electronic records of several FDA-regulated industries have to be compliant with the standards set out in FDA 21 CFR Part 11 Compliance to prove that these are authentic, safe and trustworthy. The operative factor is that the FDA has to consider these signatures as being on par with those done on paper.

Which industries are included in FDA 21 CFR Part 11 Compliance?

FDA 21 CFR Part 11 Compliance applies to nearly all FDA-regulated industries, including but not restricted to:

• Medical device manufacturers
• Drug makers
• CROs
• Biotech companies, and
• Biologics developers

The Aim of FDA 21 CFR Part 11 Compliance

The aim of FDA 21 CFR Part 11 Compliance is to ensure that specified FDA-regulated industries such as those mentioned above (with specific exceptions) implement controls -which could include audits, audit trails, documentation, system validations, and electronic signatures -for software and systems involved in processing electronic data that are:

• Required to be maintained by the FDA predicate rules or
• Used to demonstrate compliance to a predicate rule. The FDA describes a predicate rule as any requirement set forth in the Federal Food, Drug and Cosmetic Act, the Public Health Service Act, or any FDA regulation other than Part 11. FDA 21 CFR Part 11 Compliance also applies to submissions made to the FDA in electronic format, such as a new drug application.

Which industries are exempt from FDA 21 CFR Part 11 Compliance?

Interestingly, exceptions are allowed within the same industry, based on the format of filing. For example, while FDA 21 CFR Part 11 Compliance applies to submissions made to the FDA in electronic format; it does not apply to a paper submission for the same made in electronic format, such as fax.

Also, FDA 21 CFR Part 11 compliance is not required for record retention for trace backs by food manufacturers. Similar to the logic used in the mode of filing as noted above; most food manufacturers are not otherwise explicitly required to keep detailed records, but when organizations keep electronic documentation for HACCP and similar requirements; this documentation must meet these requirements.

Going by the FDA 21 CFR Part 11 Checklist is a good way to stay on track

Going by the FDA 21 CFR Part 11 Checklist is a good way to stay on track

Key Takeaway:

It makes sense for organizations that are part of 21 CFR Part 11 to have a checklist of requirements, as this helps eliminate thorny issues.

There is considerable confusion about the requirements of electronic signatures set out by 21 CFR Part 11. Many organizations get confused about areas like the mode of signatures, as there are different requirements for electronic and paper formats of the same regulation. In order to resolve confusion arising out these and other issues, making an FDA 21 CFR Part 11 checklist is a good solution.

The benefits of charting out an FDA 21 CFR Part 11 checklist are many:

• It acts as a guideline in helping organizations comply with the requirements set out in this regulation;
• It helps to overcome oversight, as there is a fairly high possibility of its occurrence;
• It helps to put necessary and appropriate regulatory requirements and standards in place to tackle the huge list of requirements in this regulation.

Going by this checklist is of immense value to organizations

The numerous advantages of EHRs notwithstanding; some concerns abound about its usage.

Electronic Health Records -an understanding

Electronic Health Records -an understanding

Key Takeaway:

EHRs are a shining example of the advancements being made in the technology the American healthcare system uses. They need to be comprehended properly to facilitate their adaption.

The terms Electronic Health Record (EHR) is self-explanatory: it signifies an electronic version of paper medical records of a patient. Since these are digitized records; they are real time, with instant access and updating over all the sources and locations at which it is available. If a new value gets entered or deleted or altered; the same gets updated at all locations. This means that any authorized user having access to a patient’s EHR gets the latest record, making decision-making easier and faster.

Features/advantages of electronic health records

• Electronic Health Records contain all details of a patient’s medical history, such as diagnosis, medication routine, treatments advised, immunization protocols and related information
• Gives importance to processes, because of which it gives access to evidence-based tools which help healthcare providers take important decisions about a patient’s care. It ensures accuracy of diagnoses and health outcomes irrespective of which medical center or healthcare professional is attending to the patient;
• In totally automating and streamlining provider workflow, EHRs make patient information instant and current across all locations, no matter in which geography that record is being accessed;
• It brings about an improvement in the quality, as well as convenience of patient care;
• Fosters increases patient participation;
• Since electronic health records are spread across the length and breadth of the country; they improve practice reduce costs.

Concerns about EHRs

The numerous advantages of EHRs notwithstanding; some concerns abound about its usage.

The EHR Incentive Program is what it is -an incentive for healthcare providers to digitize

The EHR Incentive Program is what it is -an incentive for healthcare providers to digitize

Key Takeaway:

The Centers for Medicare & Medicaid Services (CMS) are involved in a mammoth task of digitizing patient health records. They use the bait of incentives to accelerate the process while maintaining quality.

Digitizing health records is a mammoth task by any standards, considering the extent, size and nature of records that need to be made available in electronic format. To ensure that this becomes a national, pan-US activity; the federal government introduced a method by which to implement EHRs: by offering incentives to those professionals, eligible hospitals, and Critical Access Hospitals (CAHs) at various stages of adopting, implementation or upgrade, or if they have demonstrated meaningful use of certified EHR technology within set deadlines. Meeting deadlines is a very critical requirement of the EHR Incentive Program.

Criteria for being eligible for EHR incentive program

The Centers for Medicare & Medicaid Services (CMS), which oversees the EHR Incentive Program, has put forth many criteria for eligibility for EHR Incentive Programs

Thirdly, FDA 21 CFR Part 820 requires the manufacturer to establish and maintain procedures for the receipt, review, and evaluation of complaints.

What should records of investigation contain?

Records of investigation should contain the following:

• Identifiers related to the device and reported event
• If Medical Device Reporting is made, it should investigate the following:
  • Whether there were any specifications the device failed to meet
  • Whether it was for treatment or for diagnosis that the device was being used
  • In what way the device was related to the reported event, if applicable

Effective Complaint Handling Guidelines serve as a basis for improvements in medical devices

Effective Complaint Handling Guidelines serve as a basis for improvements in medical devices

Key Takeaway:

Far from being frowned upon, complaints should serve as an opportunity for medical device manufacturers to understand the customer’s expectations better and lead to improvements in the product quality.

The FDA describes a complaint as “any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution”.

FDA’s complaint handling guidelines are critical for ensuring that an organization maintains safety with regard to the medical devices they manufacture. Errors in medical devices can result in complaints, and improper handling of complaints can lead to problems for the patient, ranging from injury to fatality.

It is to prevent these problems that the FDA has issued complaint handling guidelines. FDA’s thinking is based on the reasoning that a complaint may be an indicator of serious safety, but implementing effective complaint handling guidelines can greatly mollify the gravity of the issue. It is also the first step to initiating new product development, which in turn has the potential to greatly reduce risks associated with noncompliance.

Regulations in place

Provisions relating to effective complaint handling provisions are contained in FDA 21 CFR Part 820 and GxP regulations.

Firstly, these complaint handling guidelines require medical device manufacturers to maintain complaint files. Manufacturers have to make this the first step towards establishing a sustainable complaint management system.

Secondly, Section 198 of Part 820 warrants the following:

Thirdly, FDA 21 CFR Part 820 requires the manufacturer to establish and maintain procedures for the receipt, review, and evaluation of complaints.

What should records of investigation contain?

Records of investigation should contain the following:

• Identifiers related to the device and reported event
• If Medical Device Reporting is made, it should investigate the following:
  • Whether there were any specifications the device failed to meet
  • Whether it was for treatment or for diagnosis that the device was being used
  • In what way the device was related to the reported event, if applicable