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

When a medical device fails to meet these standards for precision and accuracy

All medical devices have their stated intended use. With time, many of them undergo changes with use. Because of this, they need to be calibrated to retain their effectiveness. The FDA’s medical device calibration requirements have been devised with the same intention.

Although the FDA has medical device calibration requirements, many of these medical devices do not have specific measures that need to be set. So, in view of this, the FDA can only require that the core quality needed for the medical device’s function -the ability to meet its intended use -is met from time to time.


The FDA’s code of regulations for medical device calibration requirements

The FDA has a code of regulations for medical device calibration requirements: Part 820 of its QSR, Section 72. 21 CFR Part 820.72, which deals with inspection, measuring, and test equipment; states that medical device calibration requirements shall cover the control of these aspects of the medical device. It broadly states that manufacturers have to ensure that “…all inspection, measuring, and test equipment, including mechanical, automated, or electronic inspection and test equipment, is suitable for its intended purposes and is capable of producing valid results”.

Further, it also requires medical device manufacturers to have procedures in place for calibrating, inspecting, checking and maintaining equipment. Also included in these procedures are provisions relating to how to handle, preserve and store equipment.

Medical device calibration requirements in relation to calibration

As for calibration requirements in particular, the FDA’s medical device calibration requirements require medical device companies to have procedures in place that specifically offer directions and limits with regard to precision and accuracy. When a medical device fails to meet these standards for precision and accuracy; the FDA will evaluate if these have the potential to cause harm in the form of adverse effect on the patient. If these are discovered, the manufacturer has to calibrate the medical device to improve quality till the standards are met. All these procedures are to be documented.

Medical device calibration requirements in relation to standards

On the question of standards, in the absence of standards specifically meant for medical device calibration requirements; the FDA states that relevant international, national, state or local standard have to apply. In the absence of any of these; the company has to form its own set of standards for meeting medical device calibration requirements.


Documentation of medical device calibration

Part 21 CFR 820.72 of the FDA clearly states that the medical device manufacturer has to document all the points of calibration such as the date on which the device was identified and taken up for calibration, the name of the staff who did this, and when the next calibration is due. All these records have to be made publicly available to designated staff in the medical device company. All these form part of the FDA’s medical device calibration requirements.

FMEA in medical devices can work better when mated with ISO 14971

Failure Mode and Effects Analysis (FMEA) is a core aspect of risk management and risk analysis in medical devices. FMEA is essentially about analyzing the reasons for which a problem arises and the effects it has on the system. In the field of medical devices, it is absolutely critical to understand the failure mode and effects because the consequences of not doing this can be disastrous and many times, even fatal.

Required, but not clear about the steps

The FDA only broadly states that risk management has to be built into the manufacturing process. This leaves medical device manufacturers in a kind of quandary, because although the FDA is clear about the requirement for risk management; there is no clear-cut guideline on how this needs to be carried out. This leaves the implementation of FMEA in medical devices something that is at the discretion of the medical device company.

The FDA’s Final Rule on cGMP Quality System Regulation (QSR) is, to quote its own words, “less prescriptive and gives the manufacturer the flexibility to determine the controls that are necessary to be commensurate with risk” ( In other words, there is no specific guideline on risk management, using which medical device manufacturers can decide the ways and processes of implementing risk management. The guideline is all the more vague about risk analysis approaches and procedures like FMEA.

Complementarity with ISO 14971Since the guidelines on medical devices FMEA are rather general medical device companies that implement FMEA have to go by a buzzword: implementing FMEA at every level. In this regard, they can work complementarily with ISO 14971, whose guidelines relate to risk management.

CISOs map out their cybersecurity plan for 2018

When Omar F. Khawaja compiled his priority list for 2018, he didn’t include which security technologies he wanted or how many IT staff he hoped to hire.

Instead, the CISO at Highmark Health — a healthcare management and insurance provider whose portfolio includes Allegheny Health Network, United Concordia Dental and Visionworks, among others — articulated an overarching strategy on how the cybersecurity plan should fit within the national organization’s business strategy.


“While I do realize that I will need technology to enable many of the things I’m trying to do [this] year and going into 2019, my goal isn’t to deploy technology, but to realize certain outcomes,” said Khawaja, who works out of Highmark’s Pittsburgh headquarters.

Khawaja broke his cybersecurity plan down into five key areas of focus.

First, he wants to look at how his team makes decisions. “There are always more opportunities to make more impact and add more controls than there are the resources and time to do so,” he said. “So how do we create a decision-making framework so we get [our priorities in order]? And we’re not doing things because it’s a shiny object, but instead because it [has] real business impact?”

Second is organizational change management. The corporate security team needs to be confident that staff throughout Highmark Health, and its subsidiaries, adapt practices and processes to maximize the value of the implemented security protocols and technologies.

Next, Khawaja wants to ensure his team’s cybersecurity plan is aligned with the top business risks, so that the cybersecurity program “isn’t a security program but a risk-management program.”

The healthcare organization also wants to focus on operational excellence and customer satisfaction. “We absolutely have to understand what objectives we’re trying to achieve and who our key stakeholders are,” Khawaja said. “It’s not that we just simply secure the place, but we do it in a way that’s excellent. We have to do it at 100%, and we’ve got to be at 100% every single time.”

While Khawaja’s plans may sound ambitious, he is not alone. Studies show that executives increasingly recognize that a cyberattack could cripple their operations and mean millions in lost business and reputational damage as well as in cleanup costs. The National Association of Corporate Directors’ 2017-2018 Public Company Governance Survey found that cybersecurity threats ranked among the top five trends expected to have the greatest effect on business in the upcoming year.

For Continuation

Food Production Is A Modern Agricultural Miracle So Why Is It Under Attack

Agriculture is under attack. Environmentalists label modern farming as unsustainable, blaming farming for polluting the planet and destroying the climate. But today’s food is abundant and nutritious—a modern agricultural miracle.

From 1961 to 2013, world population more than doubled from 3.1 to 7.2 billion. But agricultural output more than tripled over the same period, according to data from the United Nations. We are slowly winning the battle against world hunger. The percentage of chronically undernourished people has fallen from 30 percent of world population in 1950 to about 11 percent today.


Not only the quantity, but the quality and variety of food are much better than in past ages. A 2015 study at Stockholm University compared modern food to recipes from the chef of King Richard II of England in the 1300s. The study concluded that people of today’s developed nations eat better than the kings of old.

In the 1300s, King Richard did not have pepper, cinnamon, cloves and nutmeg, which came to Europe from the Far East in the 1400s. He did not have coffee, which was first brewed in Arabia in the 1400s. He did not have oranges, corn, or pineapple, which arrived in Europe from Asia and North America during the 1400s and 1500s. Today we enjoy dozens of varieties of fruits, vegetables, and meats that were not available in past ages.


Today’s foods are a product of thousands of years of efforts to cultivate more abundant and more nutritious crops. Cross-pollination of plants, cross-breeding of animals, and now genetic engineering of plants and animals continues to deliver rising farm output with better food quality and variety. Grains, fruits, vegetables, meats, dairy products, and even seafood continue to improve due to advanced farming techniques.

But environmental groups attack modern farming methods as unsustainable, scorning the farmer’s use of water, land, pesticides and energy. A 2010 UN Environmental Programme document states:

Agricultural production accounts for a staggering 70% of global freshwater consumption, 38% of the total land use, and 14% of the world’s greenhouse gas emissions…The use of agrochemicals is related to ecotoxicity, eutrophication and depletion of phosphorus stocks. Intensive agriculture is related to substantial energy use. The loss of soil and biomass carbon can contribute to climate change.

The attacks on agriculture are too numerous to address in a single article, but one aspect of modern agriculture is not well known. Farmers are now giving land back to nature.

According to UN data, land used for farming is now declining. Total world agricultural area, the sum of crop land and pasture land, peaked in 2000 at 4.95 billion hectares and declined about one-half percent through 2013. Over the same period, world agricultural production increased 37 percent. The recent decline in total farm land use occurred despite 41.3 million hectares added for biofuel production, an area larger than Germany.

Full enhanced post here

Who oversees the trial, has to undertake to the FDA

A vital document required when carrying out a clinical trial is FDA Form 1572 Statement of Investigator. It is a contract between the Principal Investigator (PI) and the FDA. FDA Form 1572, or just 1572, has all details of the subjects in the research, as well as the commitments the PI, who oversees the trial, has to undertake to the FDA. This commitment concerns meeting all the requirements from the FDA as they relate to the trial.

When the PI signs the FDA Form 1572, which relates to IND studies, or the “Statement of the Investigator, which is meant for IDE studies; she undertakes a commitment that she will comply with all the appropriate regulations and will be liable to facing legal action in the event of failing to do so. Hence, the FDA Form 1572 is a strongly legally binding document which sets out the terms of the commitment between the PI and the FDA.

The FDA has created the form 1572 with two main intentions:

It aids the FDA in gauging the PI’s suitability for overseeing the study, as it requires the latter to declare criteria related to this, such as experience and qualification. It also helps it understand the purpose of the study and the suitability of its methods to help it achieve its aims. Not only the FDA, but also the sponsor of the study can get this information from the form 1572.

Additionally, the FDA Form 1572, by taking an undertaking from the Principal Investigator that she will meet the requirements set out by the FDA during the trial; criminalizes the failure on the part of the PI to meet these conditions. It treats this as giving false statements, which empowers the agency to proceed legally against the PI under 18 USC 1001. When the sponsor selects the Principal Investigator to conduct a clinical trial as an investigational new drug (IND) that meets the criteria set out in 21 CFR 312.53 (c); this form has to be submitted.

Other documents accompanying the 1572

In addition, the following documents, which set out the general and specific responsibilities that the Investigators have when conducting a clinical trial; have to accompany the FDA Form 1572:

  • 21 CFR 312.50: contains the General Responsibilities of Investigators
  • 21 CFR 812.100: sets out the Responsibilities of Investigators for Biologics
  • 21 CFR 812.110: details the Responsibilities of Investigators for devices.

Get to understand the workings of FDA Form 1572

With the FDA Form 1572 being of crucial importance, compliance with it is not something that a sponsor or a PI can take lightly. Meeting the regulatory requirements set out in this document is in the interest of everyone concerned.

It is with the purpose of familiarizing the aspects relating to FDA Form 1572 that Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, is organizing a webinar.

The speaker of this webinar, Charles H. Pierce, a consultant in the Clinical Research/Drug-Device Development arena, will offer insights into the nature of the due diligence that investigators and their staff have to take in meeting their regulatory and legal responsibilities.

Please register for this highly educative webinar by visiting Form FDA 1572 Seriously

FDA Form 1572 contains nine statements, seven out of which begin with “I agree”. Some of the essential elements named in the 1572 include:

  • 21 CFR 50 (Protection of Human Subjects)
  • 21 CFR 56 (Institutional Review Boards)
  • 21 CFR 312 (Investigational New Drug Application/IND)
  • For Device studies, 21 CFR 812 (Investigational Device Exemptions/IDE) is added in place of 21 CFR 312.

Also, additional responsibilities are outlined in GCP Guidelines of E6 (4) and the Compliance Program Guidance Manual (CPGM) 7348.811. In addition to complying with the principles of Good Clinical Practices (GCP); the PI and sponsors are advised to also use their discretion.

At this session, the speaker will offer complete clarity on these aspects. The following areas will be covered at this webinar:

  • The Investigators role in the clinical research process
  • The difference between AEs and SAEs and the reporting requirements of the investigator
  • Why the investigator maintains a list of staff signatures?
  • Why the investigator files the signed and dated protocol?
  • Why the investigator is responsible for the IC process?
  • What is the legal language of the FDA Form 1572 or Device equivalent?
  • Why is Financial Disclosure information important?
  • What is the history of the drug / device regulations?

For updates from this please

Misinterpretation of closed Data when Treated with “Normal” Statistical Methods

Geology is among the many branches of science in which compositional data (CoDa) arise naturally. In branches such as geochemistry, compositional data seem to occur typically, when one normalizes raw data or when one obtains the output from a constrained estimation procedure, such as percentages, ppm, ppb, molar concentrations, etc.

Compositional or constrained data have proved difficult to handle statistically because of the awkward constraint that the components of each vector must sum to unity. The special property of compositional data (the fact that the determinations on each specimen sum to a constant) means that the variables involved in the study occur in constrained space defined by the simplex, a restricted part of real space.

It is important for geochemists and geologists in general to be aware of the fact that the usual multivariate statistical techniques are not applicable to compositional data. They need to have access to appropriate techniques as they emerge and become available.

Pearson was the first to point out dangers that may befall the analyst who attempts to interpret correlations between Ratios whose numerators and denominators contain common parts. More recently, Aitchison, Pawlowsky-Glahn, S. Thio, and other statisticians have developed the concept of Compositional Data Analysis, pointing out the dangers of misinterpretation of closed data when treated with “normal” statistical methods.

Learning about all elements of CoDa

A webinar from Compliance4All, a leading provider of professional trainings for all the areas of regulatory compliance, will throw light on all the important aspects of CoDa. At this session, Ricardo Valls, a professional geologist with thirty years in the mining industry, and who has extensive geological, geochemical, and mining experience, managerial skills, and a solid background in research techniques; will be the speaker.

To gain insights into CoDa, please enroll for this webinar by visiting  real case studies developedreal case studies developed

At this session, Ricardo will present several real case studies he has developed, to demonstrate the advantages of applying various aspects of the CoDa analysis in the search for and evaluation of ore bodies by comparing them with regular statistical modelling of geochemical data.

At this webinar, which will be of high value to personnel involved in mining, such as Geologists, Geochemists, Exploration Personnel, Graduate Students, and Post-Graduate Students; Ricardo will cover the following areas:

o  History of the Problem

o  The Current Situation

o  The Model

o  Normal Statistical Processing of the Data

o  Compositional Data Analysis

o  Factor and Principal Component Analysis

o  Dealing with zero and b.d.l. Values

Conclusions and Recommendations.

For more click the advantages of applying different aspects