Category Archives: General

An Upcoming EMA Public Hearing on the Safety of Quinolone and Fluoroquinolone Antibiotics

On 11th April 2018 the Pharmaceutical Journal (Vol 300, No 7912, p 201) reported that the European Medicines Agency (EMA) is to hold a public hearing on the safety of quinolone and fluoroquinolone antibiotics, as part of an ongoing Pharmacovigilance Risk Assessment Committee (PRAC) review of these medicines.

As the above chemical names might suggest, the main distinction between these two classes of compound is that the fluoroquinolone compounds contain a fluorine atom, attached to the all-carbon ring in these heterocyclic molecules, and compounds in quinolone group do not.

Concern has been growing about serious long-lasting side effects in patients after taking a quinolone or a fluoroquinolone antibiotic especially for mild infections.

The date of the hearing has been set for 13 June 2018 and the Agency has invited applications to attend from patients, researchers and health professionals — including pharmacists. Hopefully some carers have been included too, a group often overlooked.

Keep your eyes open for the findings of the hearing, which we will try to report on when the outcome is available. Will both classes of compound be of equal concern or not?

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More than a Generation of Husbanding Scarce Professional Resources

The PHARMACEUTICAL INSPECTION CONVENTION (PIC) was formed in 1970 by the 10 countries that at the time comprised the European Free Trade Association (EFTA). Some of those countries have since left the PIC and others have joined.

The initial objectives included harmonisation of Good Manufacturing Requirements (GMP) and Mutual Recognition of Inspections carried out by Inspectors from PIC countries. With the explosive worldwide growth of pharmaceutical manufacturing and related activities it was recognised that were not enough experienced Inspectors to cope with the expanding workload of inspections and associated activities.

Legal and other reasons prevented certain other countries from joining the PIC and in 1995 the PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME (PIC/S) was formed. Essentially and, one might say, cleverly, PIC and PIC/S operate jointly thereby allowing a larger group of countries to task inspectors with participating in inspections. The findings are shared as and when needed and are mutually recognised by all member countries (currently 51 as at 15 May 2018).

A PIC/S Committee and PIC/S Executive Bureau meeting took place in Geneva, Switzerland on 15-18 April 2018 and minutes of the meeting were published on 9 May 2018.

Headlines are:

  • NEW PIC/S GUIDANCE ON GMP INSPECTION RELIANCE BASED ON DRAFT BY ICMRA WITH AIM TO MAXIMISE INSPECTION RESOURCES FOR GMP COMPLIANCE OF OVERSEAS FACILITIES

  • REVISION OF PIC/S GMP GUIDE (PE 009). CHAPTERS 3, 5 AND 8 OF THE PIC/S GMP GUIDE HAVE BEEN REVISED AND WILL ENTER INTO FORCE ON 1 JULY 2018; ALONG WITH ADOPTION OF TRANSPOSITION FOR PIC/S PURPOSES OF EU GUIDANCES ON GMP EXICIPENT RISK ASSESSMENT, EXPOSURE LIMITS AND GDP FOR API

  • NEW PIC/S WORKING GROUP ESTABLISHED WITH W.H.O. TO REVISE ANNEX 2 ON BIOLOGICALS AND ATMP

  • FOCUSED STAKEHOLDER CONSULTATION FOR DRAFT PIC/S GUIDANCE ON DATA INTEGRITY

  • NEW PIC/S AIDE-MEMOIRE ON CROSS-CONTAMINATION IN SHARED FACILITIES

  • NEW PIC/S PRE-ACCESSION APPLICATION RECEIVED FROM PAKISTAN / DRAP

  • NEW PIC/S WORKING GROUPS TO BE ESTABLISHED ON WHISTLE-BLOWERS/CONFIDENTIAL INFORMANTS; QUALITY DEFECTS PROCEDURES; AS WELL AS PIC/S ASSESSMENT AND RE-ASSESSMENT PROCEDURES

  • PIC/S 2018 SEMINAR TO BE HOSTED BY US FDA IN CHICAGO AND OTHER NEWS IN THE FIELD OF TRAINING FOR GM(D)P INSPECTORS

ICMRA = International Coalition of Medicines Regulatory Authorities

GMP = Good Manufacturing Practices

API = Active Pharmaceutical Ingredient

W.H.O. = World Health Organisation

ATMP = Advanced Therapy Medicinal Products

DRAP = Drug Regulatory Authority of Pakistan

GM(D)P = Good Manufacturing (Distribution) Practices

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regulatory intelligence

Our Current Objectives

Good regulatory practice and individual professional codes require staff working in pharmaceutical regulatory affairs to be trained appropriately and to maintain their professional competences [Continuing Professional Development (CPD)].

Through our regulatory consultancy and training businesses Pharmaceutical Quality Matters and PharmaQMtraining.eu, we can provide regulatory expertise and training on pharmaceutical subjects concerning drug substances (active substances) from their discovery onwards until they become drug products (finished medicinal products/dosage forms). If an active substance is new the regulatory demands can be huge whereas if it is a known or ‘existing’ drug substance the regulatory burden will usually be much lighter unless a new method of administration or a novel formulation is involved.

Complex regulatory procedures have to be followed and satisfied before a clinical trial can begin and there are even more extensive requirements to be met in order to gain approval of an application for a Marketing Authorisation (MA) (also known as a Product Licence, particularly in the UK) to allow a specified product to be sold or supplied to patients.

In all cases the industrial Intention of medicines’ development is to produce a safe and effective product but the story does not end with the granting of a MA. Adverse events have to be monitored, this being part of the major effort put into the regulatory topic of Pharmacovigilance.

For each particular approved medicine there is also the need for life-cycle management to keep any given product up to the required quality, safety and efficacy standards whilst recognising that commercial considerations and maintenance of supply may also be key factors.

In this site’s Blog Posts and also through the LinkedIn group Pharmaceutical Regulatory Training we will try to focus our writings on regulatory intelligence impacting on medicines’ development with a focus on new legislation and new guidelines and other relevant guidance from ICH and various national/multinational bodies in order to see how and where these may have an impact on the licensing and life-cycle management of new medicines. Contributions and analytical comments from readers will be welcomed especially where they enhance the training potential offered by these activities.

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Interesting times – new series of posts coming to help you

Many of you who visit this Blog because you have an interest in Pharmaceutical Regulatory Affairs may think we live in challenging and possibly interesting times. Certainly Brexit has serious potential to muddy the relatively clear waters in which we have been navigating in our careers whilst in the EU.

Soon, some things are bound to change but so far, apart from knowing that the European Medicines Agency is being relocated from London to Amsterdam, little clarity is close to hand.

Pharmaqmtraining.eu, which might even have to contemplate its own name change although we hope not, will endeavour to continue providing you with useful insight to help you in your regulatory careers.

Going forward we propose to help you with useful and regular commentary on changes to pharmaceutical regulatory subjects and practices. Keep an eye open for our communications from whatever channels we can legally use. Such methods will include messages to you if

  1. you are signed up to the Pharmaceutical Regulatory Training group on LinkedIn, or
  2. if you have ‘signed up’ on the PharmaQMtraining.eu mailing list in line with the soon to be compulsory GDPR in full to receive messages from us. You can do this by completing the Opt-In form 

For those of us who maintain interests in pharmaceutical activities predominantly in the United Kingdom we may be exposed to more changes than others who might need only to understand what affects EU countries. Either way, stay in touch with us please and we will do our best to keep you informed with helpful news.

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Improvements to the European Medicines Agency (EMA) Website

In response to feedback from users of its human regulatory website, the EMA has simplified the main navigation menu.  The initial links correspond to the key medicinal product lifecycle stages:

 

Selecting one of these links will take the user both to an overview for the chosen key stage and also to a sub-menu of other active links relevant to the chosen stage.

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Before we embark on some new regulatory updating:

Let us consider some stress management ideas, forwarded to me by a friend!

A young lady (but if you like, it could have been a young man!) confidently walked around the room while leading and explaining stress management to an audience with a raised glass of water.  Everyone knew she was going to ask the ultimate question, “half empty or half full?”

She fooled them all! “How heavy is this glass of water?” she inquired with a smile.

Answers called out ranged from 8 oz. to 20 oz.
She replied, “The absolute weight doesn’t matter.  It depends on how long I hold it. If I hold it for a minute, that’s not a problem.  If I hold it for an hour, I’ll have an ache in my right arm.

If I hold it for a day, you’ll have to call an Ambulance.  In each case it’s the same weight, but the longer I hold it, the heavier it becomes.”

She continued, “and that’s the way it is with stress.  If we carry our burdens all the time, sooner or later, as the burden becomes increasingly heavy, we won’t be able to carry on.”

“As with the glass of water, you have to put it down for a while and rest before holding it again.  When we’re refreshed, we can carry on with the burden – holding stress longer and better each time practised.”

“So, as early in the evening as you can, put all your burdens down.  Don’t carry them through the evening and into the night.  Pick them up tomorrow.”

  1. Accept the fact that some days you’re the pigeon, and some days you’re the statue!
  2. Always keep your words soft and sweet, just in case you have to eat them.
  3. Always read stuff that will make you look good if you die in the middle of it.
  4. Drive carefully… It’s not only cars that can be recalled by their Maker.
  5. If you can’t be kind, at least have the decency to be vague.
  6. If you lend someone £20 and never see that person again, it was probably worth it.
  7. It may be that your sole purpose in life is simply to serve as a warning to others.
  8. Never buy a car you can’t push.
  9. Never put both feet in your mouth at the same time, because then you won’t have a leg to stand on.
  10. Nobody cares if you can’t dance well.  Just get up and dance.
  11. Since it’s the early worm that gets eaten by the bird, sleep late.
  12. The 2nd mouse gets the cheese.
  13. When everything’s coming your way, you’re in the wrong lane.
  14. Birthdays are good for you.  The more you have, the longer you live.
  15. Some mistakes are too much fun to make only once.
  16. We could learn a lot from crayons.  Some are sharp, some are pretty and some are dull.  Some have weird names and all are different colours, but they all have to live in the same box.
  17. A truly happy person is one who can enjoy the scenery on a detour.
  18. Have an awesome day and know that someone has thought about you today.

AND MOST IMPORTANTLY

19.  Save the earth….. It’s the only planet with chocolate!  I THINK !!!!

 

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Obtain Free Access to a Vital Regulatory Resource for Pharmaceutical and Other Professionals

The EDQM (or in full, the European Directorate for the Quality of Medicines & HealthCare) maintains the Standard Terms Database, which holds the official European list of terms and definitions for describing Pharmaceutical Dose Forms, Routes and Methods of Administration, Containers, Closures and Administration Devices.

Standard Terms are to be used in the Marketing Authorisation Application, the Summary of Product Characteristics (SmPC), and in labelling and electronic communications.

They are currently provided in the Database in 33 languages from around the world: Albanian, Bosnian, Bulgarian, Chinese, Croatian, Czech, Danish, Dutch, English, Estonian, Finnish, French, German, Greek, Hungarian, Icelandic, Italian, Kazakh, Latvian, Lithuanian, Macedonian, Maltese, Norwegian, Polish, Portuguese, Romanian, Serbian, Slovak, Slovene, Spanish, Swedish, Turkish and Ukrainian.

The Database content includes combinations of terms, for example to describe where two or more items are packaged together, or where a pharmaceutical dose form and a container are described using a single term. The Database also contains patient-friendly terms, which are generally shorter terms that, where justified and authorised by the competent authority, may be used on certain labels where space is limited.

Originally a printed publication, from 1 January 2016, all approved Standard Terms and their definitions and translations can be found online in the Standard Terms database maintained by EDQM.

The database requires a registration, but is open and free for all users. The registration takes place on the EQDM website. If you do not already have an account you can set one up for free. Start by searching for https://www.edqm.eu/register/ or use your browser to search for “EDQM HelpDesk Publications Registration”.

Once you are registered select the free access link for the Standard Terms Database, complete details as necessary and your password will be emailed to you by the EDQM.

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An interesting legal result regarding off-label use; one to watch

Article from Reuters

A U.S. judge on Friday barred the U.S. Food and Drug Administration from stopping Irish drugmaker Amarin Corp from promoting its fish oil drug for off-label uses, saying the company is protected by the First Amendment.
The pharmaceutical industry has been watching this case because it is one of the first to raise a First Amendment argument in defense of promoting drugs for uses the FDA has not approved. Shares of Amarin rose 12 percent on Nasdaq.
The order by U.S. District Judge Paul Engelmayer in Manhattan means Amarin can promote its Vascepa pill to doctors for off-label use as long as it does so truthfully.

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Do you know the answers?

An API manufacturer (“Mumbai Pharma Substances”) based in India wants to export an active substance from Mumbai to

(i) Kenya and to

(ii) France.

What steps should Mumbai Pharma Substances take / have taken to ensure that these export sales proceed smoothly in the context of recent regulatory changes in the European Union?

A drug product (dosage form) manufacturer based in France wants to purchase an active substance from Mumbai Pharma Substances and take delivery at the French factory site.  Two delivery routes are being considered:

(i)  air freight by direct flight from Mumbai to France, followed by secure storage at the French airport pending road transport with direct delivery to the French factory,

(ii ) air freight by direct flight from Mumbai to the UK, with secure storage first at the UK airport and then at a MHRA-licensed UK facility pending onward transport by road directly to the French factory.

What issues come to your mind concerning compliance with the recent regulatory changes in the European Union?

A Marketing Authorisation Holder in the UK has approval to manufacture its generic product in India and in Germany, for the purpose of supplying the UK market.

Compare and contrast the regulatory issues that affect each of these two sources, in the context of recent regulatory changes in the European Union.

Does your Company source APIs from outside the EU (i.e. from a third country)?  When it comes to sourcing APIs what is meant by listed and non-listed third countries?  Where can I find the list and which countries are listed?

What is a written confirmation?

What is an Atypical Active Substance?

My company’s risk assessment against the use of the excipient lactose has concluded that this is high risk.

As part of the company’s risk mitigation procedure, I need to carry out an audit of the manufacture of this material.  Which audit standard can I use for this which will be acceptable to the inspector?

The company uses sodium benzoate as a preservative in one of the oral liquid products which we manufacture.  As our requirement is only 15 kg per year we source this excipient via a UK distributor.  However as this distributor refuses to identify the actual manufacturer I am unable to perform the required risk assessment on this material.  What should be my actions in this case?

My Company uses the same grade propylene glycol as an excipient in pharmaceutical products which are used both topically and parenterally.

The risk assessment concludes that this excipient is both ‘low risk’ and ‘high risk’ simultaneously.  How to I approach this with the supplier?

I am importing from South Korea a cellulosic material which meets the requirements of the PhEur and using it as the active component of an ophthalmic product for the treatment of ‘dry eye’.  The manufacturer will not guarantee that the material is manufactured in accordance with GMPs for active pharmaceutical ingredients, but does certify that it is manufactured in accordance with appropriate excipient GMPs.  What are my options?

“What are the main changes with the directive for the wholesale supply chain?”

“What policy do you support with regard to the checking of goods to ensure no counterfeits enter the UK wholesale supply chain?”

“What principles do you support on the product pack and coding for the unique identifier?”

“What are the significant challenges and cost implications for wholesale suppliers in adopting the new legislation?”

My company only purchases a small quantity of API each year from broker based in the UK who in turn purchases the API from an Indian API manufacturer. Do I need to audit both the broker and the manufacturer?

The API manufacturer has already been inspected by both the FDA & Danish authorities; do I still need to do an on-site audit?

“The API company in India will only allow a one day audit; what are my options?”

“As a QP what do I need to know about my API suppliers before I certify that the drug product is suitable for release?”

“Will all generic medicines end up needing to carry the tracking device and tamper evident seal?”

“Can a track & trace system that relies on an EU wide IT system ever work quickly enough in practice?”

Is a UK only system for track & trace possible?

Please use the links on our site at http://www.pharmaqmtraining.eu/brochures/falsified_medicines.html to learn more about the Course, which is confirmed to proceed in London on Thursday 27th February 2014.  There is information available on the main subject areas of the training, on the excellent panel of speakers and on the delegate package, which is priced to be attractive.  You will find it easy to make your booking and you should definitely not delay if you want to secure a place.  Delegate numbers will have to be finalised soon, so act now to avoid disappointment.  

We look forward to meeting you and to sharing a lively programme with good sessions dealing with your questions.

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