Monday, February 26, 2018

Difference between Fumigation and Fogging

Fumigation and fogging are very important processes in cleanroom area to minimize and
control the microbial load.

To keep the controlled area from being
contaminated in pharmaceuticals, two
processes namely fumigation and fogging are
used. Both the processes are used for the
same purpose, but the difference between
fumigation and fogging in pharmaceuticals is
great. Moreover, fumigation is banned in few
pharmaceuticals because of its negative effects
while fogging is a safer option than the former.
It is very important to know both the processes
to thoroughly understand the differences. In
fumigation, formaldehyde solution is mixed with
the potassium permanganate in a fixed
proportion. This mixing of formaldehyde with
potassium permanganate gives rise to fumes,
which are very effective in killing bacteria,
fungus, and their spores. This is one of the
most preferred ways of controlling the
While fumigation involves spraying formaldehyde
and potassium permanganate in liquid form,
fogging uses the mixture of hydrogen peroxide
and silver ion solution to control the
contamination. Fogging also requires a fogger
machine, which effectively fills the space with
the fogging solution. There are many different
disinfectants used as the fogging solution but
the above mentioned are most commonly
Nowadays, fogging is used more than
fumigation. As mentioned earlier, this is due to
the negative side effects of fumigation.
Fumigation involves formaldehyde solution,
which is carcinogenic or simply known as
cancer causing solution. The user has the risk
of getting infected with cancer and that is one
of the main reasons as to why fumigation is
banned. Apart from causing cancer, the
formaldehyde solution also causes the user
irritation in the eyes and nose, dizzy head, and
Other than the negative side effects, fumigation
also requires a lot of cleaning up after the
process is implemented. After the process of
fumigation in the controlled area, there is a
requirement of de-fumigation in that area too.
This generally requires air handling unit, also
known as AHU, which has to be continuously
run for a few hours in order to remove the
residues from the air. Also, mopping and
cleaning of the equipment and the area are
also needed after fumigation.
While fumigation has so many drawbacks,
fogging is completely safe. The fogger machine
simply sprays the hydrogen peroxide and silver
ion solution in the form of the aerosol in the
controlled area. Also, there is no risk to the
personnel handling the equipment and there is
no need of cleaning and moping or any other
activity like de-fogging after the process. It is
completely safe and the residues in the air
decompose with water and nascent oxygen.
To conclude, obviously fogging is a better and
safe method to control the contamination in
pharmaceuticals. With the grave difference
between them, fogging is the one which is more
preferred in the two as it is safe for the
personnel and no extra work is required. The
hydrogen peroxide and silver ion solution kills
bacteria and fungus without any difficulty and
there is no need of taking care of the residues,
unlike in the process of fumigation, where
regular care is required to keep the area as well
as the personnel handling equipment safe.
Therefore, fogging is preferred between

Wednesday, July 26, 2017

Pharmacovigilance Interview Questions and Answers

What is Pharmacovigilance?
Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medications, biological products, herbalism and traditional medicines.

What is the minimum criterion required for a valid case?
An identifiable reporter
An identifiable patient
A suspect product
An adverse drug event

What is an Adverse Drug Event (ADE) ?
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

What is an Adverse Drug Reaction (ADR) ?
An adverse drug reaction is a “response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function.” Note that there is a causal link between a drug and an adverse drug reaction. In sum, an adverse drug reaction is harm directly caused by the drug at normal doses, during normal use.

What is the basic difference between an ADE and ADR ?
There may not be a causal relationship between a drug and an ADE, whereas, there is a causal link between a drug and an adverse drug reaction.

When do you consider an event to be serious ?
If an event is associated with any one of the following, it is considered to be serious.
Life threatening
Hospitalization or prolongation of hospitalization.
Congenital anomaly
Medically significant or Important Medical Event
Required Intervention to Prevent Permanent Impairment or Damage (Devices)

Name the regulatory authorities in USA, UK, Japan and India ?
USA : United States Food and drug administration (USFDA).
UK : Medicines & Health Care Products Regulatory Agency (MHRA)
Japan : Pharmaceuticals and Medical Device Agency (PMDA)
India : Central Drugs Standard Control Organization (CDSCO)
Australia : Therapeutic Goods Administration
Canada : Health Canada
GVP Guidelines ? Total 16 Modules present, which replaces VOL 9A.

When do you consider a case to be medically confirmed?
A case is considered to be medically confirmed if it contains at least one event confirmed or reported by an HCP (Health Care Professional)
Note: HCP can be a Physician, Nurse, Pharmacist, Coroner or psychologist (only in Germany).

What do you mean by causality ?
Causality is the relationship between a set of factors. In Pharmacovigilance, causality is the relationship between the suspect product and the adverse drug reactions, like Related, Unrelated and Possible.

Name some data elements in ICSR ?
Patient demographics : Age, gender and race.
Suspect product details : Drug, dose, dosage form, therapy dates, therapy duration and indication. Adverse event details: Event, event onset date, seriousness criterion, event end date and latency.

What should a Safety narrative consist of ?
A narrative should consist of precise and concise information about the source of report, patient demographics, patient’s medical history, concomitant medications, suspect product details and adverse event details in an orderly manner.
This vary to type of reports like Spontaneous, Clinical trial and Literature and as per the Sponsor conventions as well. In upcoming article, we would share a full article of Safety Narrative.

What do you mean by MedDRA : Medical Dictionary for Regulatory Activities.
14. Explain the hierarchy in MedDRA :
System Organ Class (SOC)
High Level Group Term (HLGT)
High Level Term (HLT)
Preferred Term (PT)
Lower Level Term (LLT)

Abbreviations : Common terminology used in day to day PV Activities
a) SUSAR : Suspected Unexpected Serious Adverse Reaction
b) SAE : Serious Adverse Event
c) CIOMS : Council for International Organizations of Medical Sciences
d) ADE : Adverse Drug Event
e) SSAR : Suspected Serious Adverse Reaction
f) ADR : Adverse Drug Reaction
g) ICSR : Individual Case Safety Report
h) PSUR : Periodic Safety Update Report
i ) ICH : The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
j) HIPAA : Health Insurance Portability and Accountability Act
h) ESTRI : Electronic Standards for the Transfer of Regulatory Information.
ICH Guidelines : ICH-Efficacy Guidelines, E2A to E2F
E2A : E2A guidelines give standard definitions and terminology for key aspects of clinical safety reporting. It also gives guidance on mechanisms for handling expedited (rapid) reporting of adverse drug reactions in the investigational phase of drug development.
E2B : E2B guidelines for the maintenance of clinical safety data management and information about the data elements for transmission of Individual Case Safety Reports.

18. E2D :This document provides a standardised procedure for post-approval safety data management including expedited reporting to relevant authority. The definitions of the terms and concept specific to post-approval phase are also provided.

19. E2E : Pharmacovigilance Planning, This Guideline is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug (in this Guideline, the term “drug” denotes chemical entities, biotechnology-derived products, and vaccines). The main focus of this Guideline is on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of license application.

20. E2C : This document gives guidance on the format and content of safety updates, which need to be provided at intervals to regulatory authorities after products have been marketed. The Guideline is intended to ensure that the worldwide safety experience is provided to authorities at defined times after marketing with maximum efficiency and avoiding duplication of effort.

Thursday, March 30, 2017

Guidelines for Pharmaceutical Stability Study

Following are the guidelines for stability study conduction for new products:

1.  Formal stability study should consist of accelerated and long term stability testing on at least two primary production batches for stable drug products and in case of the susceptible drug products at least three primary production batches should be considered.

2.  The accelerated stability testing data at 40°C / 75% for minimum six months and long term stability testing data at 30°C / 65% for minimum 12 months should be available at the time of submission for new drug application and can be continued further..

3.  The product stable for 6 months at 40°C / 75% (Accelerated stability conditions) then it can be assigned the shelf life of 24 months.

4.  If the shelf life period exceeding the 24 months is to be assigned for the product the real time stability data should be available.

5.  Though not accepted internationally, as internal policy decision we can give the shelf life of 36 months if product is found stable at accelerated stability conditions of 40°C / 75% for 12 months.

6.  The shelf life of 36 months or more can be assigned to the drug formulation after completion of long term stability study for 36 months or more.

7.  If there is change in the primary packing material the product should be treated as new product for conduction of stability studies.

8.  The stability studies should be performed on each individual strength of the drug product unless bracketing is applied.

9.  If the same product is having the different doses (different strengths) and identical production formulation, and but different production process then each should be treated as new product the stability study should be carried out separately for each of the strengths.

10.  The frequency of the testing for long term stability testing should be initial and after every 3 months over the first year, every 6 months over second year and annually thereafter through out the proposed shelf life.

11.  The frequency of the testing for accelerated stability testing should be initial 3 months and 6 months.

12.  While labeling the stability samples the terms ambient conditions or room temperature are not acceptable.

13.  The stability testing should cover chemical, physical, biological and microbiological attributes including preservative content and the testing of those attributes of the drug products that are susceptible to change during storage and are likely to influence quality, safety and or efficacy of the drug product.

14.  Out of three batches selected for stability study testing, the at least two batches should be pilot scale batches and third one can be smaller if justified.

15.  The photo stability testing should be carried out on at least one primary batch of the drug product.

HPLC related Interview Question

1. How the pH of mobile phase changes?

The pH of a mobile phase pH can change if u keep it for long hours due to the effect of CO2 from the atmosphere to affect pH.

Similarly, volatile reagents such as TFA may also selectively evaporate, thus changing the eluent pH.
A Buffer can help to reduce this effect to a certain extent.

2. Reagents used for modifying pH:

Mobile phase modifiers such as trifluoroacetic acid (TFA) or triethylamine (TEA) or Acetic Acid or Formic Acid or Ammonia or Triaryl methane can b used for this purpose.But the selection should help maintain pH  properly.
Therefore, we need buffers.

3. Effect of pH in HPLC:

The pH of your mobile phase can affect the
 Retention time and
Chromatographic peak shape issues like peak Tailing, Fronting, Shoulder etc.

4. Use of Buffers in HPLC:

A buffer is a solution that will resist a change in pH when small volumes of acid or alkali are added to it or when it is diluted with water.

Buffers are used in mobile phases to keep n maintain the pH constant after adjustment to the desired pH.

5. How to select a buffer:

For best results, use a buffer that has a pH at least 2 units away from the pKa for the analyte or eluant of interest in ur analysis.

6. Why is  Phosphoric Acid selected for pH adjustments of mobile phases:

Phosphoric acid is a weak acid compared to HCl, sulphuric acid etc .

But, the pka value for phosphoric acid is 2.12, 7.2 and 12.3. We can use for maximum  pH adjustments.Similarly, it has got a suitable UV cut-off value/Transparency.

Therefore, Phosphoric acid n its salts r used for pH adjustments or for the preparation of Buffers.

7. The effect of pH on stationary phase n chromatograms:

The column stationary phase is also affected by pH. At very low pH (<2) the bonded stationary phase will be stripped from the silica support. At high pH (>8) the silica itself will be damaged by dissolution.

If the pH of the mobile phase is too close to the analyte’s pKa, you might observe split peaks or shoulders.