FWQRC, Quality Professionals

QUALITY PROFESSIONALS

Hi, Greetings from FWQRC……………..

Today’s topic is about how Quality professionals help organisations to deliver. We explain who they are and how they go about it

  • Everyone in an organisation is responsible for quality – from the CEO to the intern. But not everyone can be a quality expert. It’s important to have people who can provide the knowledge, tools and guidance to help everyone else play their part in pursuing excellence.These people are called quality professionals. Their job is to make sure organisations deliver.
  • Quality professionals come in many guises. Some are generalists, some are specialists. Many will have titles such as quality manager, quality engineer, quality director or assurance manager, while others deal with quality as part of a broader remit. Some are concerned with the delivery of products and services, while some are part of the leadership of an organisation. Some are employed in-house, while others work outside the organisations they deal with.
  • What unites quality professionals is their dedication to protecting and strengthening their organisations by making sure that stakeholders’ needs are met – and ideally, that their expectations are exceeded.

What quality professionals do

To put quality at the heart of their organisations, quality professionals focus on three specific areas, or competencies:

  • Strong governance: This starts with top management expressing a commitment to quality. Effective governance means making sure that the aims of management are crystal clear, that they reflect the requirements of stakeholders, and that the right people, policies and processes are in place to turn them into action.
  • Proper assurance: This ensures that the policies and priorities that have been decided on are being carried out properly, and that whatever is being produced – whether it’s a product, service, or project – is meeting stakeholders’ needs.
  • A culture of improvement: This means continually evaluating the organisation’s performance to improve efficiency, eliminate waste, reduce risk, respond to changes and create new opportunities.

The measure of a quality professional’s success is how well we

  • Protect reputation: avoiding the potentially catastrophic risks of getting things wrong
  • Enhance reputation: maximizing value for our customers and stakeholders
  • Improve profitability: eliminating unnecessary cost and waste and growing revenue
  • Drive change: contributing to the ongoing improvement of the organisation

Quality professionals are recognized by colleagues as

  • Agents for change: transforming processes, behaviour and culture
  • Guardians: protecting the business by identifying appropriate standards for business performance and assuring that they are met
  • Collaborators: working closely with leaders and managers
  • Leaders: creating, managing and improving the organisation’s business process systems
  • Progressive: understanding the realities of managing organisations in dynamic environments
  • Holistic: looking across business functions and hierarchies to advocate a broad process and customer-centric view of the organisation
  • Professional at FWQRC: qualified by professional institute (CQI), the CQI, and bound by a rigorous code of conduct.

Thank you for viewing FWQRC blogs….

FWQRC, GMP, Life Sciences, Pharma

Need for a proactive approach-To protect our loved one and also to continue the business without financial drop down.

We have heard the presence of NDMA impurities in Sartans and Ranitidine drugs. Initially it was only sartans, later Ranitidine and what’s next now?

Now let’s extend the concept to OTC drugs that may contain Nitrosamines impurity. Lets us review the sources of Nitrosoamines.

  1. Solvents:

The source for nitroso amines may also be from solvents.

DMF: NDMA can also be formed from Dimethyl formamide as shown below.

DMA is present as an impurity in DMF, a precursor in the industrial DMF process. It may also formed as a degradant during storage of the solvent.

DEA:

Similar to DMA formation, DEA could be formed by degradation of triethylamine (TEA) or exist as impurity in TEA raw material.

Some common organic solvents (e.g. NMP which could give rise to 4- (methyl)(nitroso)amino)butanoic acid = NMBA) and amine bases (e.g. diisopropylamine = DIPEA which could give rise to N-Nitrosodiisopropylamine (DIPNA) and N-Nitrosoethylisopropylamine (EIPNA)) would present such risks.

  • Reagents Like piperazine, a secondary amine, reacts slowly with NOx in the presence of O2 to form a nitrosamine derivative under conditions similar to those found in industrial amine-based post-combustion CO2 capture processes.

The genotoxic and mutagenic assessment is at most performed for Raw materials, reagents, catalysts etc., But do we really assess the Recycled solvents, reagents and catalysts and this may be chance for nitrosamine formation due to the presence of amines in the waste streams sent for recovery and the subsequent quenching of these materials with nitrous acid to destroy residual azide, without adequate control of nitrosamine formation or adequate purification.

Examples of recycled materials observed to be contaminated with nitrosamines include orthoxylene and tributyltin chloride (used as a source of tributyltin azide). Nitrosamines may be entrained if they have similar boiling points or solubility properties to recovered materials depending on how recovery and subsequent purification takes place (e.g. aqueous washes or distillation).

Simple checks during the manufacturing process can identify the impurities and avoids the market recall.

  1. Evaluate the solvents, reagents for the structural alert that are similar like nitrosoamines.
  2. Recovered solvents, recovered materials that are outsourced by a third party vendor.
  3. Evaluation of drug product formulation and process.

In-depth analysis during drug development should actually identify all the issues.

Budding and Small-scale industries who cannot identify the sources of the impurity or who cannot have sufficient capacity to analyse the drugs can take the help of qualified labs/ consultancies as a onetime activity.

Best advice is our cost saving should not cost the life of our fellow citizens.

A proactive approach for the high market value molecules to avoid any surprise in the future.

OTC Drugs

  • Drugs that contains Piperazine ring are Ranolazine, Trimetazidine, Amoxapine, Amoxapine, Befuraline, Buspirone, Flesinoxan, Ipsapirone, Nefazodone, Piberaline, Tandospirone, Trazodone, Vilazodone, Zalospirone, Meclozine, Cinnarizine, Hydroxyzine, Cetrizine, Levo citrizine, Niaprazine, Fluphenazine, PERPHENAZINE, Prochlorperazine, THIOTHIXENE, Quipazine, Imatinib, Benzylpiperazine, Buclizine, Ziprasidone,Etc…

Out of the above drugs listed, The OTC drugs are Cetirizine, Hydroxyzine etc are into the consideration of Nitrosoamine impurities and other prescription should also be taken into consideration.

  • One of the article which was published in the year 2001, has concluded that nitrosoamine was detected in the patients urine, who is consuming the long term treatment with Omeprazole, a Proton pump inhibitor.

Omeprazole, with the maximum daily dose of 360 mg/day is prescribed for some patients with Zollinger-Ellison Syndrome for treatment period longer than 5 years.

Since, these OTC drugs are easily available in the market and consumed without doctors prescription, there is a quick need for evaluation and control of   these impurities in the Drug substance as well as drug product.

The above statement is just an example and further evaluation is REQUIRED.

Since the method for the detection of the nitrosamines is available, why delay, start assessing and perform a risk assessment for your drugs.

Assess, Analyse, Announce your results and be responsible for public health, since these are OTC drugs.

FWQRC, GMP, Life Sciences, Pharma

NDMA-Genotoxic Impurity

Hello Readers!!!

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Today’s discussion is about the hottest topic in the pharmaceutical industry, where many industries producing the Ranitidine and Valsartan drugs recalled the batches from the MARKET due to the presence of this impurity in the drug above the acceptance criteria.

First of all, What is NMDA and NDEA impurity?
N-Nitrosodimethylamine (NDMA), also known as dimethylnitrosamine (DMN) and N-nitrosodiethylamine, the member N-nitrosoamine class is a semi-volatile organic chemical, produced as a byproduct in chemical synthesis or as a whole.

A bit more about NDMA & NDEA impurities.

NDMA

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NDEA

Nitrosodiethylamine.svg

Numerous studies were conducted in vitro in bacterial and mammalian cells, there has been overwhelming evidence that NDMA is not only a mutagenic but also clastogenic. The NDMA impurity increased the frequencies of gene mutations, chromosomal damage, sister chromatid exchange, and unscheduled DNA synthesis in a wide variety of cell types including human and rodent cells.

The evidence of genetic effects has also been observed in in vivo studies. Clastogenic effects (e.g., micronuclei, sister chromatid exchange, chromosomal aberrations) in, bone marrow cells, spleen cells and peripheral blood lymphocytes, as well as in oesophageal, kidney cells have been observed in rodents (rats, mice, or hamsters) administered NDMA either orally or by intraperitoneal injection.
Evidence of genotoxicity (e.g., chromosomal aberrations, micronuclei, gene mutation,DNA strand breaks) has also been observed in the offspring of hamsters and mice.

How does it reacts with the human body?
NDMA is metabolized by CYP2E1 enzyme in the liver, which hydroxylates one methyl group. The resulting hydroxymethyl nitrosamine is unstable and decomposes to formaldehyde, which is also used to quantify the metabolic rate and methane-diazonium-ion, which methylates DNA and protein or reacts with water to methanol. The electrophilic intermediates produced by metabolic activation of nitrosamines, react rapidly with cellular nucleophiles and target for carcinogens during tumor initiation.

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The discussion about the NDMA impurities has been conversed previously.

  • In ICH M4 guideline “ASSESSMENT AND CONTROL OF DNA REACTIVE (MUTAGENIC) IMPURITIES IN PHARMACEUTICALS TO LIMIT POTENTIAL CARCINOGENIC RISK”- Dated March 31, 2017.

  • World Health Organization Guidelines for Drinking-Water Quality, 3rd edition including 1st and 2nd addenda, 2008.

The topic is not only limited to Ranitidine and Valsartan drugs but it is applicable to all the drugs. All the drug substances should be assessed for the NDMA impurity and necessary controls should be taken.

Lets not wait for the regulatory authorities to take action upon the manufacturers. It is the Pharmaceutical manufacturers responsibility to deliver the right drugs to ensure the patient safety…

FWQRC

Right Team For The Right Job at The Right Time

All the posts related to Life Sciences and its requirements shall be updated by the technical team on daily basis.

Everyone is open to review and share your comments regarding the posts.