Good Documentation Practices Relating to USP

Good Documentation Practices (GDP) is a quintessential part of regulated manufacturing and laboratory environments. GDP has to be adhered to in the regulated industries because it is the only truly authentic method of ensuring that documents are audited and accounted for. GDP is also essential to keep track of and maintain control at all stages of the process and the product. GDP is thus a core requirement of a thoroughly developed Quality System.

US Pharmacopeia (USP) has laid out a series of GDP’s. One of the major new updates is contained in the newly proposed USP-NF General Chapter <1029>.

Basis for GDP in USPGDP for USP is also formulated on the same principle and rationale on which any GDP is built: proper, accurate and comprehensive records are the backbone to proper documentation, which is the basis for all major and minor procedures and operation.

GDP for USP has guidelines in the General Chapter 1029. These guidelines are given with the intention of helping build a foundation for the Quality Systems, apart from also ensuring the integrity and control of documents.

These GDP’s are meant for use in the production and control of the following:

  • Active pharmaceutical ingredients (APIs)
  • Medical devices
  • Excipients
  • Pharmaceutical products
  • Dietary supplements
  • Food ingredients

The General Chapter explains the justification for putting in place Good Documentation Practices in USP and helps the user evaluate and construct GMP activities.

In what areas are GDP’s listed out in Chapter 1029?GDP’s for USP are mentioned in relation to electronic and paper records, which include reports, raw data, protocol, and procedures concerning analytical data and manufacturing controls, and has recommendations on the kind of information that should be recorded for different kinds of documents that require GMP. A prominent amendment brought into the new chapter 1029 is that there is no longer a distinction between instructions and records, and all records and instructions are broadly merged into “records”.

Some broad requirements of GDP as set out in Chapter 1029USP Good Documentation Practices spell out a number of principles. Some of these include:

  • There should be clarity, accuracy, conciseness and legality of records
  • Every time an action is performed, there should be a documentation
  • Anyone dealing with documents should not backdate or postdate any action
  • The initial of the person who carried out a change should attest her initials and offer an explanation whenever an amendment is made

Electronic or manual records should go by the following GDP’s:

  • Any data entry should be traced back to the person who did the entry
  • Shorthand notations are not allowed
  • Controls should be put in place to ensure integrity of the record
  • When a thermal paper is used, a verified copy of its accuracy should be retained, and the user should initial it with the date

Brain back-up start-up ‘will be the death of users’

Nectome has said it will one day be capable of scanning the human brain and preserving it, perhaps running a deceased person’s mind as a computer simulation.

However, its current process requires a fresh brain.

The product is “100% fatal”, the team behind it told MIT Technology Review.

The company is backed by Y Combinator, an organisation that picks a group of new companies each year to fund and mentor in the hope they receive major funding further down the line.

According to the company’s website, Nectome claims it will one day be possible to survey the brain’s connectome – the neural connections within the brain – to such a detailed degree that it will be able to reconstruct a person’s memories even after they have died.

“Imagine a world where you can successfully map and pinpoint a specific memory within your brain,” the site reads.

“Today’s leading neuroscience research suggests that it is possible by preserving your connectome.”


Grant money

Nectome will be part of Y Combinator’s demo days next week – an event where start-ups pitch their new companies to an audience of investors and journalists.

Previous Y Combinator firms include Dropbox and AirBnB.

The firm is also backed by a $960,000 (£687,000) grant from the US National Institute of Mental Health, which said it saw a “commercial opportunity” in brain preservation.

According to MIT Technology Review, the team has consulted lawyers familiar with California’s relatively new laws on dignified end-of-life measures.

The company plans to focus on working with terminally ill people in the testing phase.

The company uses an embalming process to preserve minute details of the brain in microscopic detail.

Its work won a prize for furthering the field of brain preservation when it tried the method on a rabbit.

Taking that further, the team said it had already attempted its technique on a just-deceased woman in Portland, Oregon.

However, even a delay of just a couple of hours meant the brain was already badly damaged, it said.

The next stage is to find someone planning to die via doctor-assisted suicide.

To continue the link for you here

The EU’s Pharmacovigilance Directive

Pharmacovigilance is a major public health initiative of the EU. It is aimed at reducing the risk attendant in any part of the production, marketing and supply chain of medicinal products. Monitoring is done not only before the medicinal products enter the market; it is done at every stage after, too.

The aim of putting a strict vigilance regimen is to help detect any aspect of a medicinal product that could compromise on its safety. This whole system of monitoring is called pharmacovigilance.

The EU’s Pharmacovigilance Directive is the legal structure that spells out the objectives and implementation plans for the EU’s pharmacovigilance system. The Pharmacovigilance Directive is part of the EU’s efforts to enforce very stringent assessment of all medical products for their safety, quality and efficacy before they become authorized.

Regulation on all areas of medicineIn essence, the Pharmacovigilance Directive lays out the conditions and rules by which medicinal products have to be marketed within the EU and beyond. It prescribes the manner in which products have to be manufactured, labelled, marketed, recalled and destroyed. The Pharmacovigilance Directive, which applies to products for human use, bans any medicinal product that is not authorized by any member state of the EU from being marketed.

The review of 2010The Pharmacovigilance Directive underwent a major revision in 2010, by which a new legislation came into effect. The legislation passed that year further fortifies and streamlines the system relating to the safety of medicines that enter the European market.

The Pharmacovigilance Directive of 2010 strategizes areas relating to preventing, detecting and assessing of adverse reactions in patients to ensure improved patient safety and with it, public health. One of the major features of this amendment is that patients are empowered to directly report adverse drug reactions to the designated competent authorities. Another important aspect is that the definition of an adverse reaction has been widened to include issues like overdose and medication errors.

Important features of the Pharmacovigilance Directive of 2010The Pharmacovigilance Directive of 2010 seeks to take concrete steps to enhance its core objectives of patient safety and public health. It is built on these foundations:

  • It puts in place a robust, proportionate and proactive risk management regimen
  • It enhances safety data quality
  • It strengthens the link between safety evaluations and actions from regulatory authorities
  • The Pharmacovigilance Directive of 2010 has led to greater communication, transparency and patient involvement
  • It assigns clear-cut responsibilities and tasks for everyone concerned
  • It facilitates the decision-making apparatus within the EU
  • The Pharmacovigilance Directive of 2010 has established The Pharmacovigilance Risk Assessment Committee, a new scientific committee to be based at the European Medicines Agency (EMA).

When coliform bacteria are detected in drinking water

For over a hundred years, the western world has used coliform as a method of testing water contamination. A quick understanding of this method of testing the level of water contamination:

Coliforms belong to a broad class of bacteria. These bacteria are found freely in our environment. The feces of humans as well as other warm-blooded animals are a source of these bacteria. Coliforms are primarily used as a method for indicating water quality. When coliform bacteria are detected in drinking water; it may be indicative of the potential presence of other harmful, disease-causing organisms. The belief is that wherever coliform bacteria are present, there are chances that other more harmful bacteria could reside with them.


Used as a first step

Pathogens, or disease causing organisms -namely virus, bacteria and protozoa -have to be eliminated from water, or they could cause a range of waterborne diseases such as dysentery, hepatitis, and giardiasis and related ones.

Since it is difficult to physically test every sample of water for specific harm-causing bacteria, protozoa and viruses, testing water for coliform is considered. This makes sense, because it is easier to further test samples that have coliform than to test every sample.

Laboratories have been adapting this method because this is relatively much, much less expensive and less time consuming to implement this method rather than look for every specific pathogen.

Moreover, most laboratories are ill equipped to handle mass testing of huge samples of water. Coliform as a method of testing water contamination is thus a useful tool, because it prevents the incurrence of huge expenses.


Effectiveness of coliform as a method of testing water contaminationThe practical advantages of using coliform as a method of testing water contamination notwithstanding; its effectiveness is open to debate. Some scientists believe that this method is too antiquated. Later methods have been proven to be more effective methods. The Environmental Protection Agency (EPA) for instance, draws up plans for containing water contamination from time to time. Using coliform as a method of testing water contamination is just one small part of these. The agency looks more to methods such as addressing contaminants as groups, which is believed to be more effective. It encourages the development of new technologies that tackle contaminants better, faster and more economically.

However, it is too early to say if these developments will signal the discontinuation of using coliform as a method of testing water contamination in the near future.

FDA inspection is not going to invite an FDA action such as a 483 or a Warning Letter

If there is one common cause for apprehension between the smallest and biggest, and the best known and least known organizations; it has to be an FDA inspection! Any organization that is subject to an FDA inspection has to get absolutely everything of everything about its activities right to a T, to such an extent that it should be sure simply all the time, through all its processes, that an FDA inspection is not going to invite an FDA action such as a 483 or a Warning Letter. This means compliance at its highest and lowest levels.


To simplify matters to an extent, the FDA has tried to be of some assistance to help in monitoring the conduct of all aspects of the conduct and reporting of organizations involved in FDA-regulated research. This has concretized in the form of the FDA’s Bioresearch Monitoring Program, or BIMO. This on-site inspection and data audit program can be used as a reference guide by industries in FDA-regulated research industries. Adherence to it is a yardstick for compliance with FDA regulations in the field.

In other words,compliance to the implementation requirements of the BIMO is a fair indicator of how well the organization comes out unscathed out of an FDA inspection. Meant for monitoring Clinical Investigators (CIs), the Institutional Review Boards (IRBs), Sponsors or Contract Research Organizations (CROs)/Monitors, and nonclinical laboratories; the BIMO spans quite a range of players in the FDA-regulated research.

What are the BIMO’s objectives?

The FDA’s Bioresearch Monitoring Program has two important objectives:

  • Protecting the welfare, rights and safety of human research subjects
  • Ensuring that the data collected by researchers is reliable and is of acceptable integrity and quality


What are the BIMO’s functions?The FDA’s Bioresearch Monitoring Program has a few functions, which research organizations that have to survive an FDA inspection could do well to comprehend. These include:

  • Clinical data auditing
  • Inspection of the ongoing clinical research
  • Subjecting nonclinical laboratories and IRBs to inspections
  • Taking steps to train, educate and implement the FDA’s Application Integrity Policy.

Understand the underlying causes that lead to an inspection

The key to passing an FDA inspection is to understand that there are strong reaons for which an FDA inspection happens. Research organizations that want to pass an FDA inspection have to get a grasp of the factors that prompt the FDA to inspect research. These include:

  • Introduction of a new technology
  • Introduction of a new product or an indication
  • Receipts of complaints by the FDA from aggrieved parties
  • CRO being a habitual non-complier

Medical Device Process Validation is the Key Part of a Quality Process

Process validation is one of the essential functions of a quality system for medical devices. Medical device manufacturers who have to stay compliant with regulatory requirements have to obtain premarket approvals (PMA), as well as premarket notifications for both new and modified existing medical devices. The key to all these is medical device process validation.

The FDA standard for medical device process validation is CFR Part 820, Section 820.75(a), according to which, “where the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures”.



The need for medical device process validation First of all, why should medical device process be validated? The rationale for this is spelt out by the FDA: “The organization shall validate any processes for production and service condition where the resulting output cannot be verified by subsequent monitoring or measurement. This includes any processes where deficiencies become apparent only after the product is in use or the service has been delivered”.

Further, medical device process validation helps in a number of ways:

  • It ensures safety of the device
  • Increases customer satisfaction and confidence in the device
  • Reduces wastage from production of medical devices, and
  • Leads to improvements in product quality, processes and design
  • Ensures adherence to product specifications
  • Most importantly, avoids a host of embarrassing and time-consuming activities such as Warning Letters, 483’s, inspections, penalties and the like.
In relation to which regulatory requirements should medical a device process be validated?A medical device process validation has to be conducted in relation to four important standards:

  • The FDA’s Quality System Regulation
  • ISO 9001:2008
  • ISO 13485:2003
  • Relevant and appropriate OSHA standards

What to validate and what not to?Although this question appears complex, the guidelines issued by the Global Harmonization Taskforce (GHTF) serve as a good indicator for this question. It states in simple and unequivocal ways that any process whose output is verifiable, and when this verification suffices and is cost effective, does not have to be validated. Every process that does not meet this criterion has to be revalidated. The Medical Device Quality Systems Manual provides more details on this matter.

When to validate a medical device process?Medical device process validation has to be done both during production and after release, depending on the product design and release. This means that medical device process validation is carried out both when a new product is being manufactured or when there is a need to revise the process, and when defects are discovered after the release into market, when the device has to be recalled and validated.

FDA’s requirements on medical device product development process

One of the most elaborate prescriptions that the FDA has relates to the medical device product development process. This is because any error at any stage of the medical device product development process can result in serious repercussions for the patient. Since nothing is to be left to chance, the FDA has a series of steps in the medical device product development process. These are aimed at ensuring that there is total control of the device from the earliest to the last stage. All these controls are put in place to ensure that the manufacturer is able to locate an error at any stage and take remedial steps.

medicalDeviceProductDevelopmentProcessStarts with design control

The starting point of the medical device product development process is the design control process. These are a set of design control-related processes that the manufacturer has to take to make sure that the device is safe and serves its intended use. The purpose of having a proper design control system in place is to ensure that the manufacturer gets the device right through every stage and to make sure that redesign is not required at any stage. Such a scenario is something that has to be avoided, because this can result in waste of huge resources and thinning of margins.

The FDA’s requirements on medical device product development processThe FDA has an entire section, the US 21 CFR 820.30 aimed at ensuring that the medical device product development process is carried out in strict conformity with the set compliance requirements.


Roughly, the FDA’s requirements for the medical device product development process as stated in US 21 CFR 820.30 seeks to put the following requirements in place from manufacturers of medical device:

Design and development planning:This is a plan in which the design and development activities are planned by the manufacturer.

Design input:This stage of the medical device product development process takes into consideration all the parameters for making the medical device successful, such as safety, performance, risk, profit and so on.

Design output:This is a set of test, specifications or processes needed to check that the device functions properly.

Design review:The stage of the medical device product development process in which the device is thoroughly checked for defects and corrected.

Design verification:This stage confirms that the device design is able to withstand a series of tests and challenges and documents the results.

Design validation:This stage uses objective means to examine the device design and confirm if the design output meets the intended use, predictably and demonstrably over a period of time.

Design changes:These are to make sure that the changes, if and when they are incorporated at any stage of the medical device product development process, are approved and implemented.

Design transfer:The transition stage from device design to production while meeting specifications.

Design history file:A complete record of the stages of the history of the design process which demonstrates that the design was carried out in compliance with design controls prescribed by regulatory authorities.