By Dr. Scott Rudge
What is the right time to perform bacterial retention testing on a sterile filter for an aseptic process for Drug Product? I usually recommend that this be done prior to manufacturing sterile product. After all, providing for the sterility of the dosage form for an injectable drug is first and foremost the purpose of drug product manufacturing.
But there are some uncomfortable truths concerning this recommendation
1. Bacterial retention studies require large samples, liters
2. Formulations change between first in human and commercial manufacturing, requiring revalidation of bacterial retention
3. The chances of a formulation change causing bacteria to cross an otherwise integral membrane are primarily theoretical, the “risk” would appear to be low
On the other hand
1. The most frequent sterile drug product inspection citation in 2008 by the FDA was “211.113(b) Inadequate validation of sterile manufacturing” (source: presentation by Tara Gooel of the FDA, available on the ISPE website to members)
2. The FDA identifies aseptic processing as the “top priority for risk based approach” due to the proximal risk to patients
3. The FDA continues to identify smaller and smaller organisms that might pass through a filter
Is the issue serious? I think so, risk of infection to patients is one of the few direct consequences that pharmaceutical manufacturers can directly link between manufacturing practice and patient safety, which is one of the goals of Quality by Design. Is the safety threat from changes to filter properties and microbe size in the presence of slightly different formulations substantial? I don’t think so, especially not in proportion to the cost to demonstrate this specifically. But the data aren’t available to demonstrate this hypothesis, because the industry has no shared database to demonstrate a range of aqueous based protein solutions have no effect on bacterial retention. There is really nothing proprietary about this data, and the only organizations that benefit from keeping it confidential are the testing labs. Sharing this data should benefit all of us. An organization like PDA or ISPE should have an interest in polling this data and then making a case to the FDA and EMEA that the vast majority of protein formulations have been bracketed by testing that already exists, and that the revalidation of bacterial retention on filters following formulation changes is mostly superfluous.
In the meantime, if you don’t have enough product to perform bacterial retention studies, at least check the excipients, as in a placebo or diluents buffer. A filter failure is far more likely due to the excipients than the active ingredient, which is typically present in much smaller amounts (by weight and molarity). By doing this, you are both protecting your patients in early clinical testing, and reducing your risk with regulators.
Friday, April 23, 2010
Wednesday, April 14, 2010
Oops, adventitious viral DNA fragments in a vaccine
by Dr. Ray Nims
On March 22, 2010, a press release from GlaxoSmithKline (GSK) announced that DNA from porcine circovirus had been detected in their rotavirus vaccine. According to GSK, the DNA ”was first detected following work done by a research team in the US using a novel technique for looking for viruses and then confirmed by additional tests conducted by GlaxoSmithKline”. As a result of this finding, the FDA “is recommending that US clinicians and public health professionals temporarily suspend the use of Rotarix as a precautionary measure. The FDA have also stated that they intend to convene an advisory committee, within approximately four to six weeks, to review the available data and make recommendations on rotavirus vaccines licensed in the USA. The FDA will also seek input on the use of new techniques for identifying viruses in vaccines.” The EMEA, on the other hand, does not appear to consider this finding to be a safety concern, citing the fact that porcine circovirus is not infectious for human cells and does not cause disease in humans.
What is porcine circovirus? Porcine circovirus (PCV) is a member of the family Circoviridae, among the smallest of the known animal DNA viruses. It is approximately 17 nm in diameter, non-enveloped, with icosahedral symmetry. The virus was originally identified as a noncytopathic contaminant of the PK-15 porcine kidney cell line (Tischer et al., Zentralblatt Bakt Hyg A 226:153-167, 1974). Like many very small, non-enveloped viruses, PCV represents a challenge for removal and inactivation.
Why is this finding coming to light now, or stated another way, why wasn’t the PCV DNA detected when the vaccine was initially tested and approved for human use? The press release wasn’t specific as to method used. It has subsequently been revealed, however, that these fragments were detected using sequence-independent amplification (deep sequencing; or as Eric Delwart calls it, metagenomics). The resulting library of amplified sequences is characterized by BLAST searching using identification algorithms. Confirmation in this case was obtained using microarray and PCR analyses. The sequencing techniques have been available for some time, and have proven useful for identification of viruses in an academic setting, though they have not been applied to safety testing of biopharmaceuticals until fairly recently due to the relatively high costs associated with the analyses.
The finding of viral DNA should not be equated with detecting the infectious virus in the product. The sequence-independent amplification, microarray, and virus-specific PCR assays used can detect viral nucleic acid, but as normally performed do not indicate whether infectious virus is present. Generally, with the possible exception of transforming viruses, it is the infectious virus that is of concern, not its DNA. Efforts to assess the presence of intact viral genomic material and of infectious porcine circovirus in this vaccine are most likely underway at this time.
The presence of the PCV viral sequences has provisionally been attributed to the use of porcine trypsin during the culture of the Vero cell substrate in which the vaccine is manufactured. The trypsin used had been gamma-irradiated to inactivate adventitious viruses prior to use. While it would be comforting to believe that the PCV DNA may simply have reflected carryover of non-infectious, lethally-irradiated PCV1 from the trypsin, the fact is that gamma-irradiation is not very effective at inactivating this small, non-enveloped virus (Plavsic and Bolin. Resistence of porcine circovirus to gamma irradiation. Biopharm Int. 14:32-36, 2001). In the case of porcine circovirus, there is little evidence to indicate that the virus is infectious or pathogenic for humans. So regardless of the outcome of the various ongoing studies, it is likely that the use of the GSK rotavirus vaccine will be re-instated after the FDA convenes and discusses the implications of this finding.
I predict that there will be more and more of this kind of revelation in the future as the sequencing techniques display stretches of viral or other contaminant DNA within samples of biopharmaceuticals. I would hate to see revelations like this impede the use of the sequencing technologies going forward, as these technologies are going to be very useful to the industry as rapid detection methods for contaminant identification.
On March 22, 2010, a press release from GlaxoSmithKline (GSK) announced that DNA from porcine circovirus had been detected in their rotavirus vaccine. According to GSK, the DNA ”was first detected following work done by a research team in the US using a novel technique for looking for viruses and then confirmed by additional tests conducted by GlaxoSmithKline”. As a result of this finding, the FDA “is recommending that US clinicians and public health professionals temporarily suspend the use of Rotarix as a precautionary measure. The FDA have also stated that they intend to convene an advisory committee, within approximately four to six weeks, to review the available data and make recommendations on rotavirus vaccines licensed in the USA. The FDA will also seek input on the use of new techniques for identifying viruses in vaccines.” The EMEA, on the other hand, does not appear to consider this finding to be a safety concern, citing the fact that porcine circovirus is not infectious for human cells and does not cause disease in humans.
Porcine circovirus
Source: Meat and Livestock Commission, UK
What is porcine circovirus? Porcine circovirus (PCV) is a member of the family Circoviridae, among the smallest of the known animal DNA viruses. It is approximately 17 nm in diameter, non-enveloped, with icosahedral symmetry. The virus was originally identified as a noncytopathic contaminant of the PK-15 porcine kidney cell line (Tischer et al., Zentralblatt Bakt Hyg A 226:153-167, 1974). Like many very small, non-enveloped viruses, PCV represents a challenge for removal and inactivation.
Why is this finding coming to light now, or stated another way, why wasn’t the PCV DNA detected when the vaccine was initially tested and approved for human use? The press release wasn’t specific as to method used. It has subsequently been revealed, however, that these fragments were detected using sequence-independent amplification (deep sequencing; or as Eric Delwart calls it, metagenomics). The resulting library of amplified sequences is characterized by BLAST searching using identification algorithms. Confirmation in this case was obtained using microarray and PCR analyses. The sequencing techniques have been available for some time, and have proven useful for identification of viruses in an academic setting, though they have not been applied to safety testing of biopharmaceuticals until fairly recently due to the relatively high costs associated with the analyses.
The finding of viral DNA should not be equated with detecting the infectious virus in the product. The sequence-independent amplification, microarray, and virus-specific PCR assays used can detect viral nucleic acid, but as normally performed do not indicate whether infectious virus is present. Generally, with the possible exception of transforming viruses, it is the infectious virus that is of concern, not its DNA. Efforts to assess the presence of intact viral genomic material and of infectious porcine circovirus in this vaccine are most likely underway at this time.
The presence of the PCV viral sequences has provisionally been attributed to the use of porcine trypsin during the culture of the Vero cell substrate in which the vaccine is manufactured. The trypsin used had been gamma-irradiated to inactivate adventitious viruses prior to use. While it would be comforting to believe that the PCV DNA may simply have reflected carryover of non-infectious, lethally-irradiated PCV1 from the trypsin, the fact is that gamma-irradiation is not very effective at inactivating this small, non-enveloped virus (Plavsic and Bolin. Resistence of porcine circovirus to gamma irradiation. Biopharm Int. 14:32-36, 2001). In the case of porcine circovirus, there is little evidence to indicate that the virus is infectious or pathogenic for humans. So regardless of the outcome of the various ongoing studies, it is likely that the use of the GSK rotavirus vaccine will be re-instated after the FDA convenes and discusses the implications of this finding.
I predict that there will be more and more of this kind of revelation in the future as the sequencing techniques display stretches of viral or other contaminant DNA within samples of biopharmaceuticals. I would hate to see revelations like this impede the use of the sequencing technologies going forward, as these technologies are going to be very useful to the industry as rapid detection methods for contaminant identification.
Wednesday, April 7, 2010
What's Your Velocity?
By Dr. Scott Rudge
With the development of very high titer cell culture and fermentation processes, downstream processing has been identified as a new bottleneck in biotechnology. The productivity of chromatography in particular, has become a bottleneck. There are two schools of thought for scaling up chromatography: in one, linear velocity (flow rate divided by column cross sectional area) is held constant; in the other, the total (volumetric) flow rate divided by the volume of the column is held constant. In the former method, the length of the column has to be held constant. In the latter method, the geometry of the column is not important, as long as the column can be packed efficiently and flow is evenly distributed. This makes the latter method more flexible, and accommodating of commercially available off the shelf column hardware packages. But does it work?
In my experience, holding flow rate divided by column volume constant between scales works very well. There is plenty of theoretical basis for the methodology as well. Yamamoto has published extensively on the reasons that this technique works. This method is also the basis for scale up described in my textbook. Here, briefly, and using plate height theory, is the theoretical basis:
The basic goal in chromatography scale up is to maintain resolution. “Resolution” is a way to describe the power of a chromatography column to separate two components. It depends on the relative retention of the components, which is fixed by the thermodynamics of the column and remains constant as long as the chemistry (the resin type, the buffer composition) remains constant. It also depends on the peak dispersion in the column, which is a function of the transport phenomena, and is only related to the chemistry by the inherent diffusivity of the molecules involved. Otherwise, it is dependent on mass transfer, flow rate, temperature, flow distribution. Treating the thermodynamics as constant, we can say:
where Rs is Resolution, and N is the number of theoretical plates. N is the ratio of the column length L to the plate height, H, so 
In liquids, H is approximately a linear function of linear velocity v, according to van Deemter, as discussed in a previous post. So we can say that H = Cv (where C= the van Deemter constant). Now, the linear velocity is the flow rate divided by the cross sectional area of the column, A, and the column volume, V, is the cross sectional area times the column length. The total flow rate (F) divided by the column volume is held constant between scales, we’ll call this constant “f”. 
This bit of mathematical gymnastics says that Resolution only depends on two fundamental properties of the scale up, van Deemter’s term “C”, which considers the dispersion caused by convection relative to mass transfer to and from a resin particle, and “f”, the flow rate relative to the column volume that is chosen. There is no need to hold column length or linear velocity constant as long as the flow rate relative to column volume is held constant. You might also notice from the math that doubling the column length has the same effect on resolution as dropping the flowrate by half. However, doubling the length costs more in terms of resin, and consumes more solvent than decreasing the flow rate (that’s for you, Mike Klein!) and increases the pressure.
The plate count analysis is very phenomenological, but it does hold up under practice (otherwise it would be abandoned). And the more delicate mathematical models predict the same performance, so confidence in this scale up model is high.
One common mistake made by those using the constant linear velocity model is in adding extra column capacity. Since most people are unwilling to pay for a custom diameter column, but base their loadings on the total volume of resin, they add bed volume by adding length. But since they are unwilling to change the linear velocity, they end up decreasing the productivity of the column (because, for example, the resolution they achieved at a smaller scale in a 12 cm long column at 60 cm/hr is now being performed in a 15 cm long column, at 60 cm/hr, therefore taking 25% more time).
If the less well known constant F/V model is used for a process involving mammalian cells, it would be imperative to explain and demonstrate this model in the scale down validation that is a critical part of the viral clearance package.
But how can you get even more performance out of your chromatography? Treating the unit operation as an adsorption step, and scaling up using Mass Transfer Zone (MTZ) concepts will be treated in a future posting.
With the development of very high titer cell culture and fermentation processes, downstream processing has been identified as a new bottleneck in biotechnology. The productivity of chromatography in particular, has become a bottleneck. There are two schools of thought for scaling up chromatography: in one, linear velocity (flow rate divided by column cross sectional area) is held constant; in the other, the total (volumetric) flow rate divided by the volume of the column is held constant. In the former method, the length of the column has to be held constant. In the latter method, the geometry of the column is not important, as long as the column can be packed efficiently and flow is evenly distributed. This makes the latter method more flexible, and accommodating of commercially available off the shelf column hardware packages. But does it work?
In my experience, holding flow rate divided by column volume constant between scales works very well. There is plenty of theoretical basis for the methodology as well. Yamamoto has published extensively on the reasons that this technique works. This method is also the basis for scale up described in my textbook. Here, briefly, and using plate height theory, is the theoretical basis:
The basic goal in chromatography scale up is to maintain resolution. “Resolution” is a way to describe the power of a chromatography column to separate two components. It depends on the relative retention of the components, which is fixed by the thermodynamics of the column and remains constant as long as the chemistry (the resin type, the buffer composition) remains constant. It also depends on the peak dispersion in the column, which is a function of the transport phenomena, and is only related to the chemistry by the inherent diffusivity of the molecules involved. Otherwise, it is dependent on mass transfer, flow rate, temperature, flow distribution. Treating the thermodynamics as constant, we can say:
The plate count analysis is very phenomenological, but it does hold up under practice (otherwise it would be abandoned). And the more delicate mathematical models predict the same performance, so confidence in this scale up model is high.
One common mistake made by those using the constant linear velocity model is in adding extra column capacity. Since most people are unwilling to pay for a custom diameter column, but base their loadings on the total volume of resin, they add bed volume by adding length. But since they are unwilling to change the linear velocity, they end up decreasing the productivity of the column (because, for example, the resolution they achieved at a smaller scale in a 12 cm long column at 60 cm/hr is now being performed in a 15 cm long column, at 60 cm/hr, therefore taking 25% more time).
If the less well known constant F/V model is used for a process involving mammalian cells, it would be imperative to explain and demonstrate this model in the scale down validation that is a critical part of the viral clearance package.
But how can you get even more performance out of your chromatography? Treating the unit operation as an adsorption step, and scaling up using Mass Transfer Zone (MTZ) concepts will be treated in a future posting.
Wednesday, March 31, 2010
How Do You Set Endotoxin Specs on API?
By Dr. Lori Nixon
For parenteral drug products, setting a specification limit for endotoxin is a relatively straightforward exercise. If you know the maximum hourly dose and route of administration, the endotoxin limit can be readily derived from the equations set out in USP<85>.
But how do you determine an appropriate limit for your API? Don’t make the mistake of applying the same limit as product (in terms of EU/mg of active). And don’t make the mistake of blindly applying the same limit as a similar API, that may be dosed differently. Since the drug product is typically a combination of active ingredient along with excipients, solvents and container components—each of which may potentially contribute to the total endotoxin level—you should account for other potential contributions and set your drug substance limits accordingly. By setting the appropriate limit in API, you avoid the risk of an endotoxin failure that doesn’t show up until your precious API has been formulated and filled into vials—a business catastrophe!
Consider the following example:
Drug product at 50 mg/mL, intended for iv delivery in adults.
For this product, the maximum human dose/hour is 250 mg, delivered as a 5 mL volume.
From USP<85>, the endotoxin limit for iv delivery is 5 EU/kg. For a 70 kg adult, this corresponds to 350 EU maximum, or 70 EU/mL.
Tabulate the potential endotoxin contributors from your drug product formulation, container and manufacturing process. Look up the endotoxin limits (specifications) for each component you listed. In some cases it’s not possible to get a hard number, but you can at least estimate or list a “worst-case”. Some components will have negligible contribution based on their low ratio of surface contact to total formulated volume (such as the needle/tubing in the fill line); or low overall volume contribution (such as an acid/base used in a titration step). In this scenario, the sum of endotoxin contributions from all components (including API) cannot exceed 350 EU. “Solve” for the allowable endotoxin contributions from the API (X, in the table).
*Notice that in the table, drug substance is shown as 60 mg/mL (as powder) even though the formulation strength was listed as 50 mg/mL. Recognize that endotoxin measurements are usually based on powder weight rather than active ingredient weight. In this example let’s assume that the API has a moisture specification of NLT 95% and purity specification of NLT 88%; so 50 mg/mL of active (in the worst-case) actually corresponds to 60 mg/mL of API powder. So a 5 mL dose may contain as much as 300 mg of API powder.
You won’t be able to nail down everything exactly, and should recognize that relying on release specifications for some of the components above will clearly result in overestimations for endotoxin contribution. For example, the specification limit for the vials may not take into account additional reduction from depyrogenation; filters would be pre-rinsed and any subsequent endotoxin contributions would be largely diluted within the total product volume; and so forth. Nonetheless, this can be a convenient and systematic way to start your evaluation from a “worst-case” standpoint.
The allowed endotoxin contribution from the API can be calculated by subtracting the sum of the other component contributions (far right column of the table) from the total of 350 EU. In this case, X = 235.7 EU. Divide by the largest amount of drug substance powder that could go into the maximum dose (in this case 300 mg), and you have the drug substance endotoxin limit (0.79 EU/mg).
Now, do a reality check: If this drug substance limit looks like it may be problematic for any reason (analytical or process capabilities), look again at the table to see other possible ways to reduce the overall endotoxin (or revisit some of the worst-case assumptions that were clearly overly exaggerated). In the example, Salt 2 appears to be a large potential contributor, with a fairly loose specification for endotoxin. It may be possible to specify a different grade of this excipient (low-endotoxin or parenteral grade). Remember that compendial grades don’t necessarily mean low-endotoxin grades or even endotoxin-controlled grades.
For parenteral drug products, setting a specification limit for endotoxin is a relatively straightforward exercise. If you know the maximum hourly dose and route of administration, the endotoxin limit can be readily derived from the equations set out in USP<85>.
But how do you determine an appropriate limit for your API? Don’t make the mistake of applying the same limit as product (in terms of EU/mg of active). And don’t make the mistake of blindly applying the same limit as a similar API, that may be dosed differently. Since the drug product is typically a combination of active ingredient along with excipients, solvents and container components—each of which may potentially contribute to the total endotoxin level—you should account for other potential contributions and set your drug substance limits accordingly. By setting the appropriate limit in API, you avoid the risk of an endotoxin failure that doesn’t show up until your precious API has been formulated and filled into vials—a business catastrophe!
Consider the following example:
Drug product at 50 mg/mL, intended for iv delivery in adults.
For this product, the maximum human dose/hour is 250 mg, delivered as a 5 mL volume.
From USP<85>, the endotoxin limit for iv delivery is 5 EU/kg. For a 70 kg adult, this corresponds to 350 EU maximum, or 70 EU/mL.
Tabulate the potential endotoxin contributors from your drug product formulation, container and manufacturing process. Look up the endotoxin limits (specifications) for each component you listed. In some cases it’s not possible to get a hard number, but you can at least estimate or list a “worst-case”. Some components will have negligible contribution based on their low ratio of surface contact to total formulated volume (such as the needle/tubing in the fill line); or low overall volume contribution (such as an acid/base used in a titration step). In this scenario, the sum of endotoxin contributions from all components (including API) cannot exceed 350 EU. “Solve” for the allowable endotoxin contributions from the API (X, in the table).
*Notice that in the table, drug substance is shown as 60 mg/mL (as powder) even though the formulation strength was listed as 50 mg/mL. Recognize that endotoxin measurements are usually based on powder weight rather than active ingredient weight. In this example let’s assume that the API has a moisture specification of NLT 95% and purity specification of NLT 88%; so 50 mg/mL of active (in the worst-case) actually corresponds to 60 mg/mL of API powder. So a 5 mL dose may contain as much as 300 mg of API powder.
You won’t be able to nail down everything exactly, and should recognize that relying on release specifications for some of the components above will clearly result in overestimations for endotoxin contribution. For example, the specification limit for the vials may not take into account additional reduction from depyrogenation; filters would be pre-rinsed and any subsequent endotoxin contributions would be largely diluted within the total product volume; and so forth. Nonetheless, this can be a convenient and systematic way to start your evaluation from a “worst-case” standpoint.
The allowed endotoxin contribution from the API can be calculated by subtracting the sum of the other component contributions (far right column of the table) from the total of 350 EU. In this case, X = 235.7 EU. Divide by the largest amount of drug substance powder that could go into the maximum dose (in this case 300 mg), and you have the drug substance endotoxin limit (0.79 EU/mg).
Now, do a reality check: If this drug substance limit looks like it may be problematic for any reason (analytical or process capabilities), look again at the table to see other possible ways to reduce the overall endotoxin (or revisit some of the worst-case assumptions that were clearly overly exaggerated). In the example, Salt 2 appears to be a large potential contributor, with a fairly loose specification for endotoxin. It may be possible to specify a different grade of this excipient (low-endotoxin or parenteral grade). Remember that compendial grades don’t necessarily mean low-endotoxin grades or even endotoxin-controlled grades.
Tuesday, March 23, 2010
Innovators and Perfectionists
by Dr. Ray Nims
In a previous posting, Leah Choi described her frustration over the lack of specific training, received during her undergraduate schooling, in aspects germane to the realities of employment within the biopharmaceutical industry. Employment in the highly regulated world of biopharmaceutical manufacturing, Quality, and Quality Control (biopharmaceutical operations) requires different skills and employee temperaments compared to employment within the research and development (R&D) world. The academic institutions would do well to consider this during the preparation of students for eventual life in the working world.
What do we mean by different skills and employee temperaments? Most of us are familiar with the Myers and Briggs personality typing instrument which looks at attibutes like intro/extraversion, sensing, intuition, etc. This instrument provides interesting and revealing information about how different people deal with the world. In addition to the qualities addressed by Myers & Brigg, however, there is a personality spectrum which I will refer to as Innovation ↔ Perfection.
In the R&D world, technical knowledge, mastery of the literature concerning a subject, and most importantly, innovation are the attributes which are essential for success. A researcher must long to travel untraveled paths, to uncover new ground, to learn and often develop methods where such may not have existed previously (i.e., to go where no man has gone before). Those who are well suited to this environment we refer to as innovators. The academic institutions are pretty good at fostering these attributes in students.
On the other hand, the highly regulated areas of biopharmaceutical operations require individuals who are capable of following set instructions time after time, documenting their work in a precise and strictly controlled manner. Innovation, improvisation, and experimentation with mature methodologies and standard operating procedures are not encouraged. A mind-set which is compatible with achieving perfect compliance with documented procedures is the key to success in this environment. Such individuals we refer to as perfectionists, as they are motivated by the desire (or if not desire, at least the requirement) to conduct their work exactly as proscribed. It is this particular set of attributes which many academic programs fail to address adequately. This leaves employers with the task of training their entry-level staff in such matters, and (as Leah mentioned in her posting) students with the sometimes shocking revelation that they are poorly prepared for this type of employment.
Are there individuals who can be successful both as “innovators” and as “perfectionists”? Undoubtedly so! It is more likely, however, that most people fit within a spectrum falling between the two temperaments. I, for instance, have always regarded myself more of a perfectionist than an innovator, happily conducting the same assay the 100th time and still trying to do a better job than the last time. I know of others who, as soon as they learn a method, are bored with it and anxious to move on to something new. These temperaments may be determined by our personalities and may not be subject to alteration. It would appear to be valuable for academic programs to try, therefore, to determine the temperaments of their students, and to provide training suitable and appropriate for both the innovators and the perfectionists. Both the students as well as the biomedical industry would benefit from a little temperament triage and curriculum adjustment done at the undergraduate level.
In a previous posting, Leah Choi described her frustration over the lack of specific training, received during her undergraduate schooling, in aspects germane to the realities of employment within the biopharmaceutical industry. Employment in the highly regulated world of biopharmaceutical manufacturing, Quality, and Quality Control (biopharmaceutical operations) requires different skills and employee temperaments compared to employment within the research and development (R&D) world. The academic institutions would do well to consider this during the preparation of students for eventual life in the working world.
What do we mean by different skills and employee temperaments? Most of us are familiar with the Myers and Briggs personality typing instrument which looks at attibutes like intro/extraversion, sensing, intuition, etc. This instrument provides interesting and revealing information about how different people deal with the world. In addition to the qualities addressed by Myers & Brigg, however, there is a personality spectrum which I will refer to as Innovation ↔ Perfection.
In the R&D world, technical knowledge, mastery of the literature concerning a subject, and most importantly, innovation are the attributes which are essential for success. A researcher must long to travel untraveled paths, to uncover new ground, to learn and often develop methods where such may not have existed previously (i.e., to go where no man has gone before). Those who are well suited to this environment we refer to as innovators. The academic institutions are pretty good at fostering these attributes in students.
On the other hand, the highly regulated areas of biopharmaceutical operations require individuals who are capable of following set instructions time after time, documenting their work in a precise and strictly controlled manner. Innovation, improvisation, and experimentation with mature methodologies and standard operating procedures are not encouraged. A mind-set which is compatible with achieving perfect compliance with documented procedures is the key to success in this environment. Such individuals we refer to as perfectionists, as they are motivated by the desire (or if not desire, at least the requirement) to conduct their work exactly as proscribed. It is this particular set of attributes which many academic programs fail to address adequately. This leaves employers with the task of training their entry-level staff in such matters, and (as Leah mentioned in her posting) students with the sometimes shocking revelation that they are poorly prepared for this type of employment.
Are there individuals who can be successful both as “innovators” and as “perfectionists”? Undoubtedly so! It is more likely, however, that most people fit within a spectrum falling between the two temperaments. I, for instance, have always regarded myself more of a perfectionist than an innovator, happily conducting the same assay the 100th time and still trying to do a better job than the last time. I know of others who, as soon as they learn a method, are bored with it and anxious to move on to something new. These temperaments may be determined by our personalities and may not be subject to alteration. It would appear to be valuable for academic programs to try, therefore, to determine the temperaments of their students, and to provide training suitable and appropriate for both the innovators and the perfectionists. Both the students as well as the biomedical industry would benefit from a little temperament triage and curriculum adjustment done at the undergraduate level.
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