Frequently asked questions FDA

Q1: When is an FDA Form 483 issued?
A: An FDA Form 483 is issued to firm management at the conclusion of an inspection when an investigator(s) has observed any conditions that in their judgment may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts. FDA investigators are trained to ensure that each observation noted on the FDA Form 483 is clear, specific and significant. Observations are made when in the investigator’s judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
Q: What is the purpose of an FDA Form 483?
A: The FDA Form 483 notifies the company’s management of objectionable conditions. At the conclusion of an inspection, the FDA Form 483 is presented and discussed with the company’s senior management. Companies are encouraged to respond to the FDA Form 483 in writing with their corrective action plan and then implement that corrective action plan expeditiously.

Q2: What is the purpose of an FDA Form 483? A: The FDA Form 483 notifies the company’s management of objectionable conditions. At the conclusion of an inspection, the FDA Form 483 is presented and discussed with the company’s senior management. Companies are encouraged to respond to the FDA Form 483 in writing with their corrective action plan and then implement that corrective action plan expeditiously. Q3: Is the FDA Form 483 intended to be an all-inclusive list of every possible deviation from law and regulation? A: No, it’s not. The FDA Form 483 is a report which does not include observations of questionable or unknown significance at the time of the inspection. There may be other objectionable conditions that exist at the firm that are not cited on the FDA Form 483. FDA investigators are instructed to note only what they saw during the course of the inspection. Companies are responsible to take corrective action to address the cited objectionable conditions and any related non-cited objectionable conditions that might exist. Q2: How is the FDA Form 483 shared with the company? A: FDA Form 483s are discussed with a company’s management at the conclusion of the inspection. Each observation is read and discussed so that there is a full understanding of what the observations are and what they mean. Q3: What are the implications of the FDA Form 483 for agency enforcement and what happens next? A: The FDA Form 483 does not constitute a final Agency determination of whether any condition is in violation of the FD &C Act or any of its relevant regulations. The FDA Form 483 is considered, along with a written report called an Establishment Inspection Report, all evidence or documentation collected on-site, and any responses made by the company. The Agency considers all of this information and then determines what further action, if any, is appropriate to protect public health

Court Ruling: Suspended Sentence and Heavy Fine for Falsifying Stability Data

A London court has sentenced a pharmaceutical company and its former director to heavy fines. The defendant had admitted to knowingly submitting falsified data to the Medicines and Healthcare products Regulatory Agency (MHRA) in order to obtain a Marketing Authorization for a product. This was preceded by extensive investigations by the authority, during which thousands of scientific data files were analyzed and reviewed. The defendant was sentenced to eight and seven months on two counts. He will not have to spend time in prison as the sentence was suspended for 18 months. However, both the defendant and the company must pay a fine of £50,000. The defendant must also pay the prosecution costs of over £80,000. A confiscation order of over £1 million, reflecting the profit from the crime, have already been confiscated. What happened? A press release dated 15 March 2024 states that "Evotrox Oral Solutions (a liquid solution containing the active ingredient levothyroxine) was licensed in 2006 in three strengths for the treatment of hypothyroidism (underactive thyroid)." As usual, the manufacturer also had to submit stability data as part of the licence application. Back in 2008, reports emerged that the product was not stable for the whole duration of the shelf-life claimed in the original licence application. The MHRA took this as an occasion to launch an investigation. During this investigation, "the company continued to submit falsified data to the MHRA to try to support the medicine’s stability and effectiveness." A comprehensive series of independent analyses by the MHRA and a detailed evaluation of the data seized from laboratory computers brought the falsifications to light. This culminated in the termination of the marketing authorisations by the MHRA in 2013 and subsequent criminal prosecution. Statement of the MHRA In the press release, Andy Morling, MHRA Deputy Director (Criminal Enforcement), emphasizes the complexity of the investigations. "Whilst the MHRA found no evidence that patients were harmed, the fact that the manufacturers were prepared to put them at risk by knowingly supplying a substandard product is very concerning." All in all, "this is a shocking case of a pharmaceutical company that thought it was above the law and was not required to uphold our stringent standards for safety, quality and effectiveness."

What is a standard operating procedure (SOP)?

in this blog I would like to share my thought process on what is standard operating procedure and containing to this blog what are the components that are needed to be considered while writing an efficient standard operating procedure A standard operating procedure is a set of written instructions that describes the step-by-step process that must be taken to properly perform a routine activity. SOPs should be followed the exact same way every time to guarantee that the organization remains consistent and in compliance with industry regulations and business standards. Standard operating procedures provide the policies, processes and standards needed for the organization to succeed. They can benefit a business by reducing errors, increasing efficiencies and profitability, creating a safe work environment and producing guidelines for how to resolve issues and overcome obstacles.

cGMP Basic Introduction

Quality of Pharmaceutical effects either positively or negatively on each citizen of every nation. 

Therefore every nation configure its own regulatory authority for example United States has regulatory authority with the name us FDA and Australia please having the name asTGA, India is having the name as CDSCO, UK is having MHRA, European is having EDQM and etc.

While speaking from business perspective the customer base in US is very high and the cost of the drugs that is manufacturers can sell for the maximum margin in US.

In this blog we will mainly focus on how us-fda things about cgmp.

Which regulatory body of the country regulates the quality of pharmaceuticals very carefully. The main regulatory standard for ensuring pharmaceutical quality is the Current Good Manufacturing Practice (CGMPs) regulation for human pharmaceuticals. Consumers expect that each batch of medicines they take will meet quality standards so that they will be safe and effective. Most people, however, are not aware of CGMPs, or how FDA assures that drug manufacturing processes meet these basic objectives. Recently, FDA has announced a number of regulatory actions taken against drug manufacturers based on the lack of CGMPs. This paper discusses some facts that may be helpful in understanding how CGMPs establish the foundation for drug product quality.

CGMP refers to the Current Good Manufacturing Practice regulations enforced by the FDA. CGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations. This includes establishing strong quality management systems, obtaining appropriate quality raw materials, establishing robust operating procedures, detecting and investigating product quality deviations, and maintaining reliable testing laboratories. This formal system of controls at a pharmaceutical company, if adequately put into practice, helps to prevent instances of contamination, mix-ups, deviations, failures, and errors. This assures that drug products meet their quality standards.

The CGMP requirements were established to be flexible in order to allow each manufacturer to decide individually how to best implement the necessary controls by using scientifically sound design, processing methods, and testing procedures. The flexibility in these regulations allows companies to use modern technologies and innovative approaches to achieve higher quality through continual improvement. Accordingly, the "C" in CGMP stands for "current," requiring companies to use technologies and systems that are up-to-date in order to comply with the regulations. Systems and equipment that may have been "top-of-the-line" to prevent contamination, mix-ups, and errors 10 or 20 years ago may be less than adequate by today's standards.

It is important to note that CGMPs are minimum requirements. Many pharmaceutical manufacturers are already implementing comprehensive, modern quality systems and risk management approaches that exceed these minimum standards.

A consumer, in pharmaceutical industry case the consumer would be a patient, usually cannot detect (through smell, touch, or sight) that a drug product is safe or if it will work. While CGMPs require testing, testing alone is not adequate to ensure quality. In most instances testing is done on a small sample of a batch (for example, a drug manufacturer may test 100 tablets from a batch that contains 2 million tablets), so that most of the batch can be used for patients rather than destroyed by testing. 

Therefore, it is important that drugs are manufactured under conditions and practices required by the CGMP regulations to assure that quality is built into the design (As it was discussed in previous blog)and manufacturing process at every step. 

Therefore the main principle of any quality system which depends majorly on 4M system that is man, machine, method, mother nature (environment).

To understand more of 4M system please go through the following paragraph

Facilities that are in good condition, equipment that is properly maintained and calibrated, employees who are qualified and fully trained, and processes that are reliable and reproducible, are a few examples of how CGMP requirements help to assure the safety and efficacy of drug products. 

Any regulatory body of any nation inspects pharmaceutical manufacturing facilities worldwide, including facilities that manufacture active ingredients and the finished product. Inspections follow a standard approach and are conducted by highly trained FDA staff. FDA also relies upon reports of potentially defective drug products from the public and the industry. FDA will often use these reports to identify sites for which an inspection or investigation is needed. Most companies that are inspected are found to be fully compliant with the CGMP regulations.

What happens website is not following cgmp regulations can be seen next blog.

What is Quality Assurance

In this blog I would like to present what is quality assurance.

Before understanding the concept of quality assurance let us explore the generic buying process of any customer.

Every  customer would like to purchase any of goods or article. In this case a customer is having certain, clear or defined expectations that it would fulfill his/ her requirements.

Say for example if our customer would like to purchase smartphone. in this case the expectation is communication and device must be useful for multi purpose.

As we all experience the uses of smartphone in current World and the smart phone is a device used  for the communication, socializing, financial transactions, gaming knowledge, taking photographs, vedios, sharing and also caring with greatest reliable durability.

if I convert the paragraph into quality terminology these requirements or expectations will be known as specifications.

As a whole if I group the above paragraph into two different specifications one is the device must be useful for multi purpose majorly communication and durability.

now if you see the terminology reliability is the major concern of any customer because he is going to spend huge amount of money on the device.

now the customer approaches a salesperson for eCommerce website we will look into how should I trust the performance of the device.

And the question comes who is going to provide the reliability are certificate of it performance to the customer.

it is none other than Quality Assurance if you see any product it will be wearing a label QC tested are a guarantee or warranty information.

simply the salesperson will show the label or tag it is guaranteed are it has some warranty are it is having some certification therefore the customer is not trusting the sales person but the document ((Bill/Receipt) or the certificate or the information card are the guarantee card or the warranty card.

now the question comes who is going to provide this reliability certificate or warranty guarantee cards. Yes, he is none other than the person who is working in quality assurance in the organisation.

therefore Quality Assurance is having authorisation to provide the information card on guarantee our warranty on the performance of the goods are articles that are being purchased by a customer.

Now the question comes is that simple to provide guarantee and warranty card to Quality Assurance guy?.

Yes this quality assurance that I will trust the other stakeholders in the company like quality control production where house purchase and his component suppliers.

the bundle of this confidence or trust will make quality assurance personal to provide certificate on its performance or warranty or guarantee of the device or goods or articles.

from a paragraph there are few words that we must remember that requirements dictations specifications are the part of customer with which is going to satisfy our fulfill his needs.

therefore the ultimate goal of any business is to satisfy the requirements are needs of the customer with ultimate performance of the services are goods provided to the customer.

Quality Assurance plays a vital role in answering the queries that would be raised by the customer Management for regulatory authorities are national governing bodies.

Now let us see some definitions.

Confidence is a belief that future events will occur in line with ones expectations, based on familiarity and prior experience. 

Trust means conferring responsibility to and relying on a person-like entity, where you place yourself in a vulnerable position

Quality Assurance

a positive declaration intended to give confidence; a promise.

confidence or certainty in one's own abilities

Quality

The totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs, therefore quality must be built in property of any product or service.

Bottom line

For any business meeting customer expectations is very much needed to survive in this competitive world.

What is PDCA Cycle

In this blog, I am going to discuss basic fundamental processPDCA Cycle, which is being used by  Quality Assurance.

PDCA cycle is having another alternative names  which were given in the following paragraph.

PDCA, sometimes called PDSA, the "Deming Wheel," or "Deming Cycle," was developed by renowned management consultant Dr William Edwards Deming in the 1950s. Deming himself called it the "Shewhart Cycle," as his model was based on an idea from his mentor, Walter Shewhart.

From name it can be understandable that it is having four faces if a elaborate PDCAplan-do-check-act and most essentially it must be remembered that it is a cyclic process which means that it helps for continual improvement in any quality system.

now I will discuss stage wise.

Before going to plan stage.

We need to understand the problem in the best possible way.

Now the question arises how could I understand the problem.

By definition the problem is meant as a matter or situation regarded as unwelcome or harmful and needing to be dealt with and overcome.

In other words the problem is the situation are the result which is not expected. Therefore from this meaning we could understand that there are two parameters should be written on the paper in 2 columns the first column must contain what is the requirement and the second column should contain what was happened (or not expected).